Critical Care, Intensive CarePhase 4CRUSADERSNCT07189091
CReep and Maintenance flUid Sodium Chloride ADministration rEduction in cRitically Ill adultS
A Phase 4 study testing Glucose 5% for fluid creep, NaCl 0.9% (normal saline) for fluid creep and PlasmaLyte as maintenance fluid in people with Critical Care, Intensive Care and Fluid Accumulation, run by University Hospital, Antwerp at 4 sites in Belgium.
Trial summary
This study is enrolling adult patients who require a prolonged stay in the intensive care unit (ICU). These patients often receive large amounts of intravenous fluids, which can contain more salt (sodium and chloride) than the body normally needs. Extra salt and water can build up in the body and may delay recovery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Critical Care, Intensive Care, Fluid Accumulation, Fluid and Electrolyte Imbalance
- What is being tested?
- Glucose 5% for fluid creep, NaCl 0.9% (normal saline) for fluid creep and PlasmaLyte as maintenance fluid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 640 participants
- Where
- 4 sitesBelgium
- Study dates
- 7 Oct 2025to 30 Jul 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years of age
- Patients who are admitted to the ICU for medical or surgical emergencies, including complications of elective surgery
- The treating physician expects the patient will still require ICU care in two days, indicating a severe or complex condition at enrollment
- The patient is expected to receive at least 300 mL of fluid creep or at least 1 liter of maintenance fluid according to study-arm during the first 24h after inclusion
Who cannot join
- A contraindication to hypotonic fluids due to risk of brain edema (including traumatic brain injury, major stroke, intracranial/subarachnoid hemorrhage, meningoencephalitis, intracranial malignancies…), with the timing and clinical judgment left at the discretion of the treating physician.
- Hyponatremia below 131 mmol/L at admission
- Admission solely for treatment of fluid accumulation due to cardiac decompensation, without other acute medical conditions requiring ICU-level care. Note: Patients with heart failure as a comorbidity, those on chronic diuretic therapy, or presenting with edema/bilateral lung infiltrates due to other conditions (e.g., sepsis, pneumonia) are not excluded.
- Patient's death is deemed imminent and inevitable, admission for palliative care or admission solely for organ donation
- Patient receiving chronic renal replacement therapy
- Patients referred after a stay of more than 24 hours in another ICU
Show all 14Show fewer
- Patients randomized in CRUSADERS before
- Patient is co-enrolled in an unapproved concomitant ICU-trial or in any trial with an intervention that affects fluid administration or fluid balance
- Additional exclusion criteria for the SALADIN nested substudy
- Patients expected to require renal replacement therapy within 24 hours
- Increased insensible fluid losses: burns, extensive wounds or skin defects or massive diarrhea,…
- Patients without a urine catheter
- Patients expected to require bladder irrigation within 24 hours
- Patients on chronic treatment with loop or thiazide diuretics (including combination preparations)
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium4 sites, 4 recruiting
- Not yet recruiting
ZAS Middelheim
Antwerp, 2020
- Recruiting
ZAS Cadix
Antwerp, 2030
- Not yet recruiting
Antwerp University Hopsital (UZA)
Edegem, 2650
- Not yet recruiting
ZAS Paflijn
Merksem, 2170
About this study
Official title: Effect of Reduced Sodium Chloride in Fluid Creep and Maintenance Fluids in Critically Ill Adults: A Randomized Controlled Trial
This study is enrolling adult patients who require a prolonged stay in the intensive care unit (ICU). These patients often receive large amounts of intravenous fluids, which can contain more salt (sodium and chloride) than the body normally needs. Extra salt and water can build up in the body and may delay recovery.
The study will test two strategies:
Read more
Fluid creep: These are fluids used to dilute medications or keep intravenous lines open. Usually, the choice is based on habit. In the intervention group, a salt-free glucose 5% solution will be used (if the responsible pharmacist confirms it is compatible with the medication).
Maintenance fluids: These fluids cover daily needs for water and electrolytes. In the intervention group, a lower-salt solution (NaCl 0.3% in glucose 3.3%) will be given, with volume decided by the treating physician.
The comparison group will receive usual care: NaCl 0.9% (commonly called "normal saline") for fluid creep, and an isotonic solution (PlasmaLyte) for maintenance fluids.
The main outcome is the number of days patients are alive and free of life support (such as ventilator or dialysis) during the first 90 days. Other outcomes include abnormal sodium, chloride, or glucose levels, fluid balance and need for diuretics, kidney injury, use of dialysis, time on the ventilator, survival, and length of ICU and hospital stay.
A smaller substudy (SALADIN) will measure in detail how the body handles sodium, chloride, and water using additional calculation on blood tests, urine collections, body weight, and bioimpedance analysis
Read the detailed description
Critically ill patients admitted to the intensive care unit (ICU) often receive large volumes of intravenous fluids. Beyond resuscitation fluids, which have been extensively studied, two other sources contribute substantially to fluid, sodium, and chloride exposure:
Fluid creep, the use of diluents and small-volume infusions to dissolve medications or maintain line patency.
Maintenance fluids, prescribed to cover daily fluid and electrolyte needs when oral intake is insufficient.
Together, fluid creep and maintenance fluids account for more than half of all intravenous fluids given in ICU patients. These fluids frequently contain supraphysiologic amounts of sodium and chloride. Because the kidneys of critically ill patients are unable to excrete these excesses efficiently, sodium and chloride accumulate, leading to positive fluid balances, electrolyte disturbances, pulmonary edema, renal dysfunction, and prolonged organ support. Observational data have linked both fluid overload and hyperchloremia to higher morbidity and mortality.
Prior research has focused mainly on resuscitation fluids. Large randomized trials comparing chloride-rich saline to balanced crystalloids demonstrated only small differences in outcomes, in part because resuscitation fluids make up a limited fraction of overall fluid exposure. In contrast, fluid creep and maintenance solutions offer a larger and modifiable source of sodium and chloride. Small studies and volunteer experiments have shown that sodium-poor maintenance fluids and sodium-free diluents reduce fluid retention and hyperchloremia, but their effect on patient-centered outcomes has never been tested in a large randomized trial.
CRUSADERS (CReep and maintenance flUid Sodium chloride ADministration Reduction in cRitically ill adultS) is a multicenter, randomized, double-blind, phase IV, low-intervention trial designed to address this evidence gap. The trial compares two strategies:
NaCl-poor arm (intervention):
Fluid creep: medications are dissolved in glucose 5% (except when another diluent is mandatory); line patency fluids are glucose 5%.
Maintenance fluids: NaCl 0.3% in glucose 3.3%, with volume determined by the treating physician.
NaCl-rich arm (control):
Fluid creep: medications are dissolved in NaCl 0.9%; line patency fluids are NaCl 0.9%.
Maintenance fluids: PlasmaLyte, with volume determined by the treating physician.
All study fluids are licensed, widely used hospital products. Blinding is achieved through repackaging into opaque study bags labeled only with trial codes. Treating teams decide indications and volumes, ensuring pragmatic applicability while isolating the effect of fluid composition.
The primary endpoint is days alive and without life support (DAWOLS) at 90 days after ICU admission, an outcome that integrates survival and duration of mechanical ventilation or renal replacement therapy. Secondary outcomes include electrolyte disorders (hyponatremia, hypernatremia, hyperchloremia), fluid balance and diuretic use, acute kidney injury, renal replacement therapy, mechanical ventilation, glycemic control, mortality, and ICU/hospital length of stay. Exploratory outcomes include biochemical markers of salt-induced catabolism such as the serum urea-to-creatinine ratio.
A nested substudy (SALADIN - SAlt baLAnce Detailed INsight) will provide mechanistic insights into sodium, chloride, and water handling. In this subgroup, detailed daily balances will be calculated from fluid intake and 24-hour urine collections, combined with measurements of free water clearance, bioelectrical impedance analysis, body weight, and volume kinetics modeling.
The trial will recruit 640 adult ICU patients across four Belgian mixed ICUs. Inclusion requires expected ICU stay >48 hours and anticipated exposure to maintenance fluids or significant fluid creep. Patients with contraindications to hypotonic fluids, severe baseline hyponatremia, imminent death, chronic dialysis, or exclusive palliative/organ donation admission are excluded.
Patients are randomized 1:1 with stratification by site, mechanical ventilation, and surgical admission. Study treatment continues throughout the ICU stay or until study fluids are no longer available according to the blinded allocation schedule (minimum 28 days after randomization). Follow-up continues until 90 days after ICU admission.
The CRUSADERS trial is investigator-initiated, funded by the Research Foundation Flanders (FWO), and sponsored by Antwerp University Hospital. It is conducted under European Union (EU) Clinical Trial Regulation (536/2014) with central review via the Clinical Trial Information System (CTIS). Given the exclusive use of approved fluids in routine indications, the trial is classified as low-intervention. A Data and Safety Monitoring Board oversees safety with predefined stopping rules and interim analysis after half the planned population has been followed.
By targeting sodium and chloride in fluid creep and maintenance solutions rather than resuscitation fluids, CRUSADERS aims to test a simple, cost-neutral, and widely applicable strategy to improve survival and reduce life support dependence in critically ill patients. If positive, the trial may provide a strong evidence base for revising international fluid therapy guidelines and daily ICU practice.
- Conditions
- Critical Care, Intensive Care, Fluid Accumulation, Fluid and Electrolyte Imbalance, Critical Illness, Fluid Balance Outcomes
- Being tested
- Glucose 5% for fluid creep, NaCl 0.9% (normal saline) for fluid creep, PlasmaLyte as maintenance fluid, NaCl 0.3% in glucose 3.3% as maintenance fluid
- Keywords
- Intensive Care Unit, Critically Ill, Critical Illness, Intravenous fluids, Maintenance fluids, Fluid Creep, Sodium chloride reduction, Salt reduction, Hypotonic fluids, Saline (NaCl 0.9%), Fluid balance, Electrolyte disorders, Glycemic control, Acute kidney injury, Mechanical ventilation, Organ support, Hyponatremia
- Medical subject headings
- Critical Illness, Acute Kidney Injury, Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucose 5% for fluid creepDrug
- Medications, including concentrated electrolytes, are dissolved in glucose 5% except when another solvent is mandatory according to the responsible pharmacist.
- Infusions to keep intravenous lines open are glucose 5%
NaCl 0.9% (normal saline) for fluid creepDrug
- Medications, including concentrated electrolytes, are dissolved in NaCl 0.9% except when another solvent is mandatory according to the responsible pharmacist.
- All infusions to keep intravenous lines open are NaCl 0.9%.
PlasmaLyte as maintenance fluidDrug
- Type: Maintenance fluid is PlasmaLyte. Potassium chloride or potassium phosphate can be added (or administered separately) whenever deemed necessary.
- Rate: at the discretion of the treating physician, typically 25-30 ml/kg of body weight with a maximum of 100 ml/hour, accounting for concomitant fluid sources such as nutrition and fluid creep. It is allowed to prescribe a higher volume of study maintenance fluids to include replacement if both study fluids are considered appropriate.
NaCl 0.3% in glucose 3.3% as maintenance fluidDrug
- Type: maintenance fluid is NaCl 0.3% in glucose 3.3%. Potassium chloride or potassium phosphate can be added (or administered separately) at the discretion of the treating physician whenever necessary.
- Rate: at the discretion of the treating physician, typically 25-30 ml/kg of body weight with a maximum of 100 ml/hour, accounting for concomitant fluid sources such as nutrition and fluid creep. It is allowed to prescribe a higher volume of study maintenance fluids to include replacement if both study fluids are considered appropriate
| Study group | Role | What they receive |
|---|---|---|
| Sodium chloride reduction strategy, the NaCl-poor arm | Active comparator | Participants receive a sodium-chloride reduction strategy during their ICU stay. Medications are diluted in glucose 5% (unless another solvent is mandatory), and intravenous line patency fluids are glucose 5%. Daily maintenance fluids are NaCl 0.3% in glucose 3.3%, with the volume determined by the treating physician. The goal is to reduce sodium and chloride exposure while maintaining fluid and electrolyte support.
Interventions:
Drug: Glucose 5% Drug: NaCl 0.3% in Glucose 3.3% Receives: Drug: Glucose 5% for fluid creep; Drug: NaCl 0.3% in glucose 3.3% as maintenance fluid |
| Isotonic fluid strategy, the NaCl-rich arm | Active comparator | Participants receive a standard isotonic fluid strategy during their ICU stay. Medications are diluted in NaCl 0.9% (unless another solvent is mandatory), and intravenous line patency fluids are NaCl 0.9%. Daily maintenance fluids are PlasmaLyte, with the volume determined by the treating physician. This reflects the common standard of care in many ICUs.
Interventions:
Drug: NaCl 0.9% Drug: PlasmaLyte Receives: Drug: NaCl 0.9% (normal saline) for fluid creep; Drug: PlasmaLyte as maintenance fluid |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days alive and without life support at day 90 (DAWOLS90)
The composite endpoint DAWOLS90 is defined as the number of days alive and without the use of life support within 90 days counted from ICU admission. Unit of measure: days. Patients who die before D90 are assigned zero days. The following life-support therapies are considered 1/ Mechanical ventilation: includes invasive and noninvasive ventilation, including continuous positive airway pressure (CPAP) but excluding high-flow nasal oxygen. Each ICU day counts as a ventilator day if support is in place. Post-extubation days are counted as ventilator-free only if no re-intubation occurs within 48 hours. 2/ Renal replacement therapy (RRT): includes continuous RRT, peritoneal dialysis, or intermittent hemodialysis (IHD). If IHD is given, periods with up to 3 days between sessions are counted as days with RRT.
Measured: From admission until day 90 counted from ICU admission (= Day 1)
Secondary outcomes (18)
Occurrence of moderate and severe hyponatremia
Defined as the number of participants with at least one episode of:
Moderate hyponatremia: serum sodium 125-129 mmol/L Severe hyponatremia: serum sodium <125 mmol/L
To be counted as an event, the sodium level must decrease by at least 3 mmol/L from baseline to reduce misclassification due to pre-existing mild hyponatremia or analytical variation. Assessments are based on daily routine morning serum sodium values from the central laboratory (ion-specific electrode). If available, paired serum albumin and point-of-care sodium values (measured within 2 hours) will be recorded to allow cross-checks and sensitivity analyses
Measured: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of moderate and severe hypernatremia
Defined as the number of participants with at least one episode of:
Moderate hypernatremia: serum sodium 151-155 mmol/L Severe hypernatremia: serum sodium >155 mmol/L
To be counted as an event, the sodium level must increase by at least 3 mmol/L from baseline to account for pre-existing mild hypernatremia and analytical variation. Assessments are based on daily routine morning serum sodium values from the central laboratory (ion-specific electrode). If available, paired serum albumin and point-of-care sodium values (measured within 2 hours of the central measurement) will be recorded to allow cross-checks and sensitivity analyses.
Measured: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of moderate and severe hyperchloremia
Defined as the number of participants with at least one episode of:
Moderate hyperchloremia: serum chloride 111-115 mmol/L Severe hyperchloremia: serum chloride >115 mmol/L
To be counted as an event, the chloride level must increase by at least 2 mmol/L from baseline to account for pre-existing mild hyperchloremia and analytical variation. Assessments are based on daily routine morning serum chloride values from the central laboratory (ion-specific electrode). If available, paired serum albumin and point-of-care chloride values (measured within 2 hours of the central measurement) will be recorded to allow cross-checks and sensitivity analyses
Measured: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Time to first administration of intravenous loop diuretic
Defined as the time (in hours) from randomization until the first administration of an intravenous loop diuretic (e.g., furosemide or bumetanide). The exact timestamp of first administration is recorded.
Measured: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Proportion of ICU days with intravenous loop diuretic use
Defined as the number of ICU days during which a participant receives at least one dose of an intravenous loop diuretic, expressed as a proportion of total ICU days.
Measured: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Cumulative fluid balance in mL up to first IV loop diuretic use
Defined as the cumulative net fluid balance, excluding insensible losses. Daily fluid balance is calculated as total inputs minus total outputs (mL per ICU day).
Inputs: study fluids, non-study fluid creep, non-study maintenance and replacement fluids, non-study resuscitation fluids, enteral and parenteral nutrition, blood products, and oral intake.
Outputs: urine output, net ultrafiltration by renal replacement therapy, gastric aspirates, drain outputs, and diarrhea (if precisely measured).
The cumulative fluid balance is the sum of all daily fluid balances from ICU admission until the morning of the first ICU day on which an intravenous loop diuretic is prescribed.
Measured: From ICU admission until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of hyperglycemia
Defined as the proportion of glucose measurements >180 mg/dL relative to the total number of glucose assessments during the ICU stay. Mean daily glucose values will also be calculated for each ICU day. Assessments are based on point-of-care blood gas analyzer values, which are routinely collected multiple times per day in all ICU patients.
Measured: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of hypoglycemia
Defined as the number of participants with at least one episode of hypoglycemia, serum glucose <70 mg/dL, measured on routine point-of-care blood gas analysis. Severe hypoglycemia (<40 mg/dL) is separately recorded as a serious adverse reaction.
Measured: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of new-onset acute kidney injury (AKI)
Defined as the number of participants who develop new-onset AKI stage 2 or 3 according to KDIGO criteria (Kidney Disease: Improving Global Outcomes), starting from the third ICU day after randomization. AKI classification is based on daily serum creatinine (central laboratory morning samples) and urine output collected every 12-24 hours. KDIGO stage 1 is not assessed in this trial.
Measured: From third ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of new-onset need for renal replacement therapy (RRT)
Defined as the number of participants requiring new initiation of RRT (continuous renal replacement therapy, peritoneal dialysis, or intermittent hemodialysis). To attribute RRT to the intervention, only events starting on or after the second ICU day following randomization are considered.
Measured: From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)
Renal replacement therapy-free days at day 90
Calculated as the number of days during the 90-day observation period that a participant is alive and not receiving renal replacement therapy (RRT). For intermittent hemodialysis, periods with up to 3 days between sessions are counted as days on RRT.
Measured: From ICU admission until day 90 counted from ICU admission.
Occurrence of new-onset need for mechanical ventilation
Defined as the number of participants who newly require mechanical ventilation after randomization. Mechanical ventilation includes invasive and noninvasive ventilation (including continuous positive airway pressure (CPAP)) but excludes high-flow nasal oxygen. To attribute events to the intervention, only new initiation from the second ICU day after randomization is considered.
Measured: From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)
Ventilator-free days at day 90
Calculated as the number of days during the 90-day observation period that a participant is alive and free of mechanical ventilation. Mechanical ventilation includes invasive and noninvasive ventilation (including CPAP) but excludes high-flow nasal oxygen. Following extubation, days are counted as ventilator-free only if no re-intubation occurs within 48 hours.
Measured: From ICU admission until ICU discharge (up to day 90 counted from ICU admission)
Days alive and out of hospital at day 90 (DAOH90)
Defined as the number of days a participant is alive and outside the hospital during the 90 days after ICU admission. If a patient is discharged and later readmitted, both admissions are included in the total number of hospitalization days. Mortality is penalized and assigned a value of zero DAOH. DAOH is calculated at day 90 counted from ICU admission.
Measured: From ICU admission until day 90 counted from ICU admission.
ICU length of stay
Defined as the number of calendar days from ICU admission to ICU discharge, including referral or transfer to other ICUs following the same admission.
Measured: From ICU admission until ICU discharge (up to day 90 counted from ICU admission).
Hospital length of stay
Defined as the number of calendar days from ICU admission to hospital discharge, including transfers to other hospitals. Discharges or transfers to rehabilitation wards within the same hospital are not counted as hospital length of stay.
Measured: From ICU admission until hospital discharge (up to day 90 counted from ICU admission)
ICU mortality
Death occurring at any time while continuously in ICU during the index (initial) ICU episode. Inter-ICU transfers are considered part of the same continuous ICU episode. Deaths after discharge from the index ICU episode-whether on the ward or during any later ICU readmission within the same hospital admission-are not counted.
Measured: From ICU admission until discharge from the index ICU episode, including any continuous referrals/transfers to other ICUs (up to day 90 counted from ICU admission)
Hospital mortality
Death occurring at any time during the index (initial) hospital admission, irrespective of location (ICU or ward within the same hospital) and including transfers to other hospitals within the same continuous admission. Deaths after discharge from the index hospital admission are not counted, even if the patient is readmitted later.
Measured: From ICU admission until discharge from the index hospital admission (up to day 90 counted from ICU admission)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2025
- Study start7 Oct 2025
- Primary completion30 Apr 2028 (estimated)
- Study completion30 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Critical Care, Intensive CareStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is an investigator-initiated, multicenter, randomized, double-blind, parallel-group phase IV trial conducted in four mixed ICUs in Belgium. Adult patients expected to require prolonged ICU care are randomized 1:1 to a sodium-chloride reduction strategy (NaCl-poor arm) or to a standard isotonic fluid strategy (NaCl-rich arm). Randomization is stratified by study site, surgical admission, and invasive mechanical ventilation at enrollment, using permuted blocks with concealed allocation. Each study arm consists of two components: composition of fluid creep (diluents and line patency solutions) and composition of maintenance fluids. All fluids are market-authorized products prepared and blinded by hospital pharmacy, supplied in opaque bags labeled only with trial codes. The assigned strategy is maintained throughout the ICU stay or until blinded study fluids are no longer available under the rotating allocation schedule. Follow-up continues until day 90 after ICU admission
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 640 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Ziekenhuis aan de Stroom, Research Foundation Flanders
- Responsible party
- Sponsor
- Investigators
- Niels Van Regenmortel, MD, PhD, Principal investigator, Ziekenhuis aan de Stroom (ZAS) Network of Hospitals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07189091
- Sponsor's protocol ID
- Edge 003813
- Other IDs
- 2025-520744-14-00, 2025
- Acronym
- CRUSADERS
- Status last verified
- Sep 2025
- First submitted
- 25 Aug 2025
- Last updated
- 3 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Granholm A, Schjorring OL, Jensen AKG, Kaas-Hansen BS, Munch MW, Klitgaard TL, Crescioli E, Kjaer MN, Strom T, Lange T, Perner A, Rasmussen BS, Moller MH. Association between days alive without life support/out of hospital and health-related quality of life. Acta Anaesthesiol Scand. 2023 Jul;67(6):762-771. doi: 10.1111/aas.14231. Epub 2023 Mar 21.
PubMed 36915265Van Regenmortel N, Verbrugghe W, Roelant E, Van den Wyngaert T, Jorens PG. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med. 2018 Apr;44(4):409-417. doi: 10.1007/s00134-018-5147-3. Epub 2018 Mar 27.
PubMed 29589054Van Regenmortel N, Moers L, Langer T, Roelant E, De Weerdt T, Caironi P, Malbrain MLNG, Elbers P, Van den Wyngaert T, Jorens PG. Fluid-induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults. Ann Intensive Care. 2021 May 17;11(1):79. doi: 10.1186/s13613-021-00851-3.
PubMed 33999276Van Regenmortel N, Hendrickx S, Roelant E, Baar I, Dams K, Van Vlimmeren K, Embrecht B, Wittock A, Hendriks JM, Lauwers P, Van Schil PE, Van Craenenbroeck AH, Verbrugghe W, Malbrain MLNG, Van den Wyngaert T, Jorens PG. 154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial. Intensive Care Med. 2019 Oct;45(10):1422-1432. doi: 10.1007/s00134-019-05772-1. Epub 2019 Oct 1.
PubMed 31576437Sakr Y, Vincent JL, Reinhart K, Groeneveld J, Michalopoulos A, Sprung CL, Artigas A, Ranieri VM; Sepsis Occurence in Acutely Ill Patients Investigators. High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest. 2005 Nov;128(5):3098-108. doi: 10.1378/chest.128.5.3098.
PubMed 16304249Silversides JA, Major E, Ferguson AJ, Mann EE, McAuley DF, Marshall JC, Blackwood B, Fan E. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med. 2017 Feb;43(2):155-170. doi: 10.1007/s00134-016-4573-3. Epub 2016 Oct 12.
PubMed 27734109Salahuddin N, Sammani M, Hamdan A, Joseph M, Al-Nemary Y, Alquaiz R, Dahli R, Maghrabi K. Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study. BMC Nephrol. 2017 Feb 1;18(1):45. doi: 10.1186/s12882-017-0460-6.
PubMed 28143505Bihari S, Prakash S, Potts S, Matheson E, Bersten AD. Addressing the inadvertent sodium and chloride burden in critically ill patients: a prospective before-and-after study in a tertiary mixed intensive care unit population. Crit Care Resusc. 2018 Dec;20(4):285-293.
PubMed 30482136Magee CA, Bastin MLT, Laine ME, Bissell BD, Howington GT, Moran PR, McCleary EJ, Owen GD, Kane LE, Higdon EA, Pierce CA, Morris PE, Flannery AH. Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study. Crit Care Med. 2018 Aug;46(8):1217-1223. doi: 10.1097/CCM.0000000000003191.
PubMed 29727367Van Regenmortel N, Langer T, De Weerdt T, Roelant E, Malbrain M, Van den Wyngaert T, Jorens P. Effect of sodium administration on fluid balance and sodium balance in health and the perioperative setting. Extended summary with additional insights from the MIHMoSA and TOPMAST studies. J Crit Care. 2022 Feb;67:157-165. doi: 10.1016/j.jcrc.2021.10.022. Epub 2021 Nov 17.
PubMed 34798374Nagae M, Egi M, Furushima N, Okada M, Makino S, Mizobuchi S. The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study. J Anesth. 2019 Apr;33(2):287-294. doi: 10.1007/s00540-019-02626-4. Epub 2019 Feb 26.
PubMed 30806785Surveillance report 2017 - Intravenous fluid therapy in adults in hospital (2013) NICE guideline CG174 [Internet]. London: National Institute for Health and Care Excellence (NICE); 2017 Apr 24. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK552079/
PubMed 31891467Haines RW, Zolfaghari P, Wan Y, Pearse RM, Puthucheary Z, Prowle JR. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019 Dec;45(12):1718-1731. doi: 10.1007/s00134-019-05760-5. Epub 2019 Sep 17.
PubMed 31531715Kitada K, Daub S, Zhang Y, Klein JD, Nakano D, Pedchenko T, Lantier L, LaRocque LM, Marton A, Neubert P, Schroder A, Rakova N, Jantsch J, Dikalova AE, Dikalov SI, Harrison DG, Muller DN, Nishiyama A, Rauh M, Harris RC, Luft FC, Wassermann DH, Sands JM, Titze J. High salt intake reprioritizes osmolyte and energy metabolism for body fluid conservation. J Clin Invest. 2017 May 1;127(5):1944-1959. doi: 10.1172/JCI88532. Epub 2017 Apr 17.
PubMed 28414295Rakova N, Kitada K, Lerchl K, Dahlmann A, Birukov A, Daub S, Kopp C, Pedchenko T, Zhang Y, Beck L, Johannes B, Marton A, Muller DN, Rauh M, Luft FC, Titze J. Increased salt consumption induces body water conservation and decreases fluid intake. J Clin Invest. 2017 May 1;127(5):1932-1943. doi: 10.1172/JCI88530. Epub 2017 Apr 17.
PubMed 28414302
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Reduced Sodium Chloride in Fluid Creep and Maintenance Fluids in Critically Ill Adults: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07189091
- Acronym / sponsor ID
- CRUSADERS / Edge 003813
- Conditions
- Critical Care, Intensive Care, Fluid Accumulation, Fluid and Electrolyte Imbalance, Critical Illness, Fluid Balance Outcomes
- Keywords
- Intensive Care Unit, Critically Ill, Critical Illness, Intravenous fluids, Maintenance fluids, Fluid Creep, Sodium chloride reduction, Salt reduction
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 640 participants (estimated)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Ziekenhuis aan de Stroom, Research Foundation Flanders
- Study start
- 7 Oct 2025 (actual)
- Primary completion
- 30 Apr 2028 (estimated)
- Study completion
- 30 Jul 2028 (estimated)
- First posted
- 23 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is enrolling adult patients who require a prolonged stay in the intensive care unit (ICU). These patients often receive large amounts of intravenous fluids, which can contain more salt (sodium and chloride) than the body normally needs. Extra salt and water can build up in the body and may delay recovery.
The study will test two strategies:
Fluid creep: These are fluids used to dilute medications or keep intravenous lines open. Usually, the choice is based on habit. In the intervention group, a salt-free glucose 5% solution will be used (if the responsible pharmacist confirms it is compatible with the medication).
Maintenance fluids: These fluids cover daily needs for water and electrolytes. In the intervention group, a lower-salt solution (NaCl 0.3% in glucose 3.3%) will be given, with volume decided by the treating physician.
The comparison group will receive usual care: NaCl 0.9% (commonly called "normal saline") for fluid creep, and an isotonic solution (PlasmaLyte) for maintenance fluids.
The main outcome is the number of days patients are alive and free of life support (such as ventilator or dialysis) during the first 90 days. Other outcomes include abnormal sodium, chloride, or glucose levels, fluid balance and need for diuretics, kidney injury, use of dialysis, time on the ventilator, survival, and length of ICU and hospital stay.
A smaller substudy (SALADIN) will measure in detail how the body handles sodium, chloride, and water using additional calculation on blood tests, urine collections, body weight, and bioimpedance analysis
Detailed description
Critically ill patients admitted to the intensive care unit (ICU) often receive large volumes of intravenous fluids. Beyond resuscitation fluids, which have been extensively studied, two other sources contribute substantially to fluid, sodium, and chloride exposure:
Fluid creep, the use of diluents and small-volume infusions to dissolve medications or maintain line patency.
Maintenance fluids, prescribed to cover daily fluid and electrolyte needs when oral intake is insufficient.
Together, fluid creep and maintenance fluids account for more than half of all intravenous fluids given in ICU patients. These fluids frequently contain supraphysiologic amounts of sodium and chloride. Because the kidneys of critically ill patients are unable to excrete these excesses efficiently, sodium and chloride accumulate, leading to positive fluid balances, electrolyte disturbances, pulmonary edema, renal dysfunction, and prolonged organ support. Observational data have linked both fluid overload and hyperchloremia to higher morbidity and mortality.
Prior research has focused mainly on resuscitation fluids. Large randomized trials comparing chloride-rich saline to balanced crystalloids demonstrated only small differences in outcomes, in part because resuscitation fluids make up a limited fraction of overall fluid exposure. In contrast, fluid creep and maintenance solutions offer a larger and modifiable source of sodium and chloride. Small studies and volunteer experiments have shown that sodium-poor maintenance fluids and sodium-free diluents reduce fluid retention and hyperchloremia, but their effect on patient-centered outcomes has never been tested in a large randomized trial.
CRUSADERS (CReep and maintenance flUid Sodium chloride ADministration Reduction in cRitically ill adultS) is a multicenter, randomized, double-blind, phase IV, low-intervention trial designed to address this evidence gap. The trial compares two strategies:
NaCl-poor arm (intervention):
Fluid creep: medications are dissolved in glucose 5% (except when another diluent is mandatory); line patency fluids are glucose 5%.
Maintenance fluids: NaCl 0.3% in glucose 3.3%, with volume determined by the treating physician.
NaCl-rich arm (control):
Fluid creep: medications are dissolved in NaCl 0.9%; line patency fluids are NaCl 0.9%.
Maintenance fluids: PlasmaLyte, with volume determined by the treating physician.
All study fluids are licensed, widely used hospital products. Blinding is achieved through repackaging into opaque study bags labeled only with trial codes. Treating teams decide indications and volumes, ensuring pragmatic applicability while isolating the effect of fluid composition.
The primary endpoint is days alive and without life support (DAWOLS) at 90 days after ICU admission, an outcome that integrates survival and duration of mechanical ventilation or renal replacement therapy. Secondary outcomes include electrolyte disorders (hyponatremia, hypernatremia, hyperchloremia), fluid balance and diuretic use, acute kidney injury, renal replacement therapy, mechanical ventilation, glycemic control, mortality, and ICU/hospital length of stay. Exploratory outcomes include biochemical markers of salt-induced catabolism such as the serum urea-to-creatinine ratio.
A nested substudy (SALADIN - SAlt baLAnce Detailed INsight) will provide mechanistic insights into sodium, chloride, and water handling. In this subgroup, detailed daily balances will be calculated from fluid intake and 24-hour urine collections, combined with measurements of free water clearance, bioelectrical impedance analysis, body weight, and volume kinetics modeling.
The trial will recruit 640 adult ICU patients across four Belgian mixed ICUs. Inclusion requires expected ICU stay >48 hours and anticipated exposure to maintenance fluids or significant fluid creep. Patients with contraindications to hypotonic fluids, severe baseline hyponatremia, imminent death, chronic dialysis, or exclusive palliative/organ donation admission are excluded.
Patients are randomized 1:1 with stratification by site, mechanical ventilation, and surgical admission. Study treatment continues throughout the ICU stay or until study fluids are no longer available according to the blinded allocation schedule (minimum 28 days after randomization). Follow-up continues until 90 days after ICU admission.
The CRUSADERS trial is investigator-initiated, funded by the Research Foundation Flanders (FWO), and sponsored by Antwerp University Hospital. It is conducted under European Union (EU) Clinical Trial Regulation (536/2014) with central review via the Clinical Trial Information System (CTIS). Given the exclusive use of approved fluids in routine indications, the trial is classified as low-intervention. A Data and Safety Monitoring Board oversees safety with predefined stopping rules and interim analysis after half the planned population has been followed.
By targeting sodium and chloride in fluid creep and maintenance solutions rather than resuscitation fluids, CRUSADERS aims to test a simple, cost-neutral, and widely applicable strategy to improve survival and reduce life support dependence in critically ill patients. If positive, the trial may provide a strong evidence base for revising international fluid therapy guidelines and daily ICU practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is an investigator-initiated, multicenter, randomized, double-blind, parallel-group phase IV trial conducted in four mixed ICUs in Belgium. Adult patients expected to require prolonged ICU care are randomized 1:1 to a sodium-chloride reduction strategy (NaCl-poor arm) or to a standard isotonic fluid strategy (NaCl-rich arm). Randomization is stratified by study site, surgical admission, and invasive mechanical ventilation at enrollment, using permuted blocks with concealed allocation. Each study arm consists of two components: composition of fluid creep (diluents and line patency solutions) and composition of maintenance fluids. All fluids are market-authorized products prepared and blinded by hospital pharmacy, supplied in opaque bags labeled only with trial codes. The assigned strategy is maintained throughout the ICU stay or until blinded study fluids are no longer available under the rotating allocation schedule. Follow-up continues until day 90 after ICU admission
| Arm | Type | Receives |
|---|---|---|
| Sodium chloride reduction strategy, the NaCl-poor arm | Active comparator | Drug: Glucose 5% for fluid creep, Drug: NaCl 0.3% in glucose 3.3% as maintenance fluidParticipants receive a sodium-chloride reduction strategy during their ICU stay. Medications are diluted in glucose 5% (unless another solvent is mandatory), and intravenous line patency fluids are glucose 5%. Daily maintenance fluids are NaCl 0.3% in glucose 3.3%, with the volume determined by the treating physician. The goal is to reduce sodium and chloride exposure while maintaining fluid and electrolyte support. Interventions: Drug: Glucose 5% Drug: NaCl 0.3% in Glucose 3.3% |
| Isotonic fluid strategy, the NaCl-rich arm | Active comparator | Drug: NaCl 0.9% (normal saline) for fluid creep, Drug: PlasmaLyte as maintenance fluidParticipants receive a standard isotonic fluid strategy during their ICU stay. Medications are diluted in NaCl 0.9% (unless another solvent is mandatory), and intravenous line patency fluids are NaCl 0.9%. Daily maintenance fluids are PlasmaLyte, with the volume determined by the treating physician. This reflects the common standard of care in many ICUs. Interventions: Drug: NaCl 0.9% Drug: PlasmaLyte |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- At least 18 years of age
- Patients who are admitted to the ICU for medical or surgical emergencies, including complications of elective surgery
- The treating physician expects the patient will still require ICU care in two days, indicating a severe or complex condition at enrollment
- The patient is expected to receive at least 300 mL of fluid creep or at least 1 liter of maintenance fluid according to study-arm during the first 24h after inclusion
Key exclusion criteria (14 listed)
- A contraindication to hypotonic fluids due to risk of brain edema (including traumatic brain injury, major stroke, intracranial/subarachnoid hemorrhage, meningoencephalitis, intracranial malignancies…), with the timing and clinical judgment left at the discretion of the treating physician.
- Hyponatremia below 131 mmol/L at admission
- Admission solely for treatment of fluid accumulation due to cardiac decompensation, without other acute medical conditions requiring ICU-level care. Note: Patients with heart failure as a comorbidity, those on chronic diuretic therapy, or presenting with edema/bilateral lung infiltrates due to other conditions (e.g., sepsis, pneumonia) are not excluded.
- Patient's death is deemed imminent and inevitable, admission for palliative care or admission solely for organ donation
- Patient receiving chronic renal replacement therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Glucose 5% for fluid creep* Medications, including concentrated electrolytes, are dissolved in glucose 5% except when another solvent is mandatory according to the responsible pharmacist. * Infusions to keep intravenous lines open are glucose 5% | Drug | Sodium chloride reduction strategy, the NaCl-poor arm |
| NaCl 0.9% (normal saline) for fluid creep* Medications, including concentrated electrolytes, are dissolved in NaCl 0.9% except when another solvent is mandatory according to the responsible pharmacist. * All infusions to keep intravenous lines open are NaCl 0.9%. | Drug | Isotonic fluid strategy, the NaCl-rich arm |
| PlasmaLyte as maintenance fluid* Type: Maintenance fluid is PlasmaLyte. Potassium chloride or potassium phosphate can be added (or administered separately) whenever deemed necessary. * Rate: at the discretion of the treating physician, typically 25-30 ml/kg of body weight with a maximum of 100 ml/hour, accounting for concomitant fluid sources such as nutrition and fluid creep. It is allowed to prescribe a higher volume of study maintenance fluids to include replacement if both study fluids are considered appropriate. | Drug | Isotonic fluid strategy, the NaCl-rich arm |
| NaCl 0.3% in glucose 3.3% as maintenance fluid* Type: maintenance fluid is NaCl 0.3% in glucose 3.3%. Potassium chloride or potassium phosphate can be added (or administered separately) at the discretion of the treating physician whenever necessary. * Rate: at the discretion of the treating physician, typically 25-30 ml/kg of body weight with a maximum of 100 ml/hour, accounting for concomitant fluid sources such as nutrition and fluid creep. It is allowed to prescribe a higher volume of study maintenance fluids to include replacement if both study fluids are considered appropriate | Drug | Sodium chloride reduction strategy, the NaCl-poor arm |
Primary outcome
Days alive and without life support at day 90 (DAWOLS90)
Time frame: From admission until day 90 counted from ICU admission (= Day 1)
The composite endpoint DAWOLS90 is defined as the number of days alive and without the use of life support within 90 days counted from ICU admission. Unit of measure: days. Patients who die before D90 are assigned zero days. The following life-support therapies are considered 1/ Mechanical ventilation: includes invasive and noninvasive ventilation, including continuous positive airway pressure (CPAP) but excluding high-flow nasal oxygen. Each ICU day counts as a ventilator day if support is in place. Post-extubation days are counted as ventilator-free only if no re-intubation occurs within 48 hours. 2/ Renal replacement therapy (RRT): includes continuous RRT, peritoneal dialysis, or intermittent hemodialysis (IHD). If IHD is given, periods with up to 3 days between sessions are counted as days with RRT.
18 secondary outcomes
Occurrence of moderate and severe hyponatremia
Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of moderate and severe hypernatremia
Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of moderate and severe hyperchloremia
Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Time to first administration of intravenous loop diuretic
Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Proportion of ICU days with intravenous loop diuretic use
Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Cumulative fluid balance in mL up to first IV loop diuretic use
Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of hyperglycemia
Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of hypoglycemia
Time frame: From randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of new-onset acute kidney injury (AKI)
Time frame: From third ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)
Occurrence of new-onset need for renal replacement therapy (RRT)
Time frame: From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)
Renal replacement therapy-free days at day 90
Time frame: From ICU admission until day 90 counted from ICU admission.
Occurrence of new-onset need for mechanical ventilation
Time frame: From the second ICU day after randomization until ICU discharge (up to day 90 counted from ICU admission)
Ventilator-free days at day 90
Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission)
Days alive and out of hospital at day 90 (DAOH90)
Time frame: From ICU admission until day 90 counted from ICU admission.
ICU length of stay
Time frame: From ICU admission until ICU discharge (up to day 90 counted from ICU admission).
Hospital length of stay
Time frame: From ICU admission until hospital discharge (up to day 90 counted from ICU admission)
ICU mortality
Time frame: From ICU admission until discharge from the index ICU episode, including any continuous referrals/transfers to other ICUs (up to day 90 counted from ICU admission)
Hospital mortality
Time frame: From ICU admission until discharge from the index hospital admission (up to day 90 counted from ICU admission)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2026.
- Background: PubMed 36915265Granholm A, Schjorring OL, Jensen AKG, Kaas-Hansen BS, Munch MW, Klitgaard TL, Crescioli E, Kjaer MN, Strom T, Lange T, Perner A, Rasmussen BS, Moller MH. Association between days alive without life support/out of hospital and health-related quality of life. Acta Anaesthesiol Scand. 2023 Jul;67(6):762-771. doi: 10.1111/aas.14231. Epub 2023 Mar 21.
- Background: PubMed 29589054Van Regenmortel N, Verbrugghe W, Roelant E, Van den Wyngaert T, Jorens PG. Maintenance fluid therapy and fluid creep impose more significant fluid, sodium, and chloride burdens than resuscitation fluids in critically ill patients: a retrospective study in a tertiary mixed ICU population. Intensive Care Med. 2018 Apr;44(4):409-417. doi: 10.1007/s00134-018-5147-3. Epub 2018 Mar 27.
- Background: PubMed 33999276Van Regenmortel N, Moers L, Langer T, Roelant E, De Weerdt T, Caironi P, Malbrain MLNG, Elbers P, Van den Wyngaert T, Jorens PG. Fluid-induced harm in the hospital: look beyond volume and start considering sodium. From physiology towards recommendations for daily practice in hospitalized adults. Ann Intensive Care. 2021 May 17;11(1):79. doi: 10.1186/s13613-021-00851-3.
- Background: PubMed 31576437Van Regenmortel N, Hendrickx S, Roelant E, Baar I, Dams K, Van Vlimmeren K, Embrecht B, Wittock A, Hendriks JM, Lauwers P, Van Schil PE, Van Craenenbroeck AH, Verbrugghe W, Malbrain MLNG, Van den Wyngaert T, Jorens PG. 154 compared to 54 mmol per liter of sodium in intravenous maintenance fluid therapy for adult patients undergoing major thoracic surgery (TOPMAST): a single-center randomized controlled double-blind trial. Intensive Care Med. 2019 Oct;45(10):1422-1432. doi: 10.1007/s00134-019-05772-1. Epub 2019 Oct 1.
- Background: PubMed 16304249Sakr Y, Vincent JL, Reinhart K, Groeneveld J, Michalopoulos A, Sprung CL, Artigas A, Ranieri VM; Sepsis Occurence in Acutely Ill Patients Investigators. High tidal volume and positive fluid balance are associated with worse outcome in acute lung injury. Chest. 2005 Nov;128(5):3098-108. doi: 10.1378/chest.128.5.3098.
- Background: PubMed 27734109Silversides JA, Major E, Ferguson AJ, Mann EE, McAuley DF, Marshall JC, Blackwood B, Fan E. Conservative fluid management or deresuscitation for patients with sepsis or acute respiratory distress syndrome following the resuscitation phase of critical illness: a systematic review and meta-analysis. Intensive Care Med. 2017 Feb;43(2):155-170. doi: 10.1007/s00134-016-4573-3. Epub 2016 Oct 12.
- Background: PubMed 28143505Salahuddin N, Sammani M, Hamdan A, Joseph M, Al-Nemary Y, Alquaiz R, Dahli R, Maghrabi K. Fluid overload is an independent risk factor for acute kidney injury in critically Ill patients: results of a cohort study. BMC Nephrol. 2017 Feb 1;18(1):45. doi: 10.1186/s12882-017-0460-6.
- Background: PubMed 30482136Bihari S, Prakash S, Potts S, Matheson E, Bersten AD. Addressing the inadvertent sodium and chloride burden in critically ill patients: a prospective before-and-after study in a tertiary mixed intensive care unit population. Crit Care Resusc. 2018 Dec;20(4):285-293.
- Background: PubMed 29727367Magee CA, Bastin MLT, Laine ME, Bissell BD, Howington GT, Moran PR, McCleary EJ, Owen GD, Kane LE, Higdon EA, Pierce CA, Morris PE, Flannery AH. Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study. Crit Care Med. 2018 Aug;46(8):1217-1223. doi: 10.1097/CCM.0000000000003191.
- Background: PubMed 34798374Van Regenmortel N, Langer T, De Weerdt T, Roelant E, Malbrain M, Van den Wyngaert T, Jorens P. Effect of sodium administration on fluid balance and sodium balance in health and the perioperative setting. Extended summary with additional insights from the MIHMoSA and TOPMAST studies. J Crit Care. 2022 Feb;67:157-165. doi: 10.1016/j.jcrc.2021.10.022. Epub 2021 Nov 17.
- Background: PubMed 30806785Nagae M, Egi M, Furushima N, Okada M, Makino S, Mizobuchi S. The impact of intravenous isotonic and hypotonic maintenance fluid on the risk of delirium in adult postoperative patients: retrospective before-after observational study. J Anesth. 2019 Apr;33(2):287-294. doi: 10.1007/s00540-019-02626-4. Epub 2019 Feb 26.
- Background: PubMed 31891467Surveillance report 2017 - Intravenous fluid therapy in adults in hospital (2013) NICE guideline CG174 [Internet]. London: National Institute for Health and Care Excellence (NICE); 2017 Apr 24. No abstract available. Available from http://www.ncbi.nlm.nih.gov/books/NBK552079/
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Niels Van Regenmortel, MD, PhD principal investigator
Ziekenhuis aan de Stroom (ZAS) Network of Hospitals
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Glucose 5% for fluid creep, NaCl 0.9% (normal saline) for fluid creep and PlasmaLyte as maintenance fluid in people with Critical Care, Intensive Care and Fluid Accumulation, run by University Hospital, Antwerp at 4 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Petra Y Vertongen (+3238214404, petra.vertongen@uza.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days alive and without life support at day 90 (DAWOLS90) (time frame: From admission until day 90 counted from ICU admission (= Day 1)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07189091, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2026.