SepsisPhase 3NCT03277677
The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients
A Phase 3 study testing Normal saline and Ringer's Acetate in people with Sepsis and Septic Shock, run by Chulalongkorn University at 1 site in Thailand.
Trial summary
The high chloride content of 0.9%sodium chloride (0.9%NaCl) leads to adverse pathophysiological effects in both animals and healthy human volunteers. Small randomized trials confirm that the hyperchloremic acidosis induced by 0.9%NaCl also occurs in patients. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Sepsis, Septic Shock, Acute Kidney Injury
- What is being tested?
- Normal saline and Ringer's Acetate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- 1 siteThailand
- Study dates
- 1 Jul 2017to 1 Mar 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old
- Who need fluid resuscitation in the Emergency Room (ER).
- Who have fulfilled the criteria for sepsis/septic shock within the previous 24 hours according to sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
- o Patients with infection and resulted from a host's systemic inflammatory response syndrome (SIRS) to infection are defined as sepsis if meet the criteria 2 or more of
- Temperature >38°C or <36°C
- Heart rate >90/min
Show all 11Show fewer
- Respiratory rate >20/min or PaCo2 <32 mm Hg (4.3 kPa)
- White blood cell count >12000/mm3 or <4000/mm3 or >10% immature bands.
- Patient who have Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.
- o Patients with septic shock can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP ≥65 mm Hg and having a serum lactate level >2 mmol/L (18 mg/dL) despite adequate volume resuscitation.
- AND where informed consent is obtainable either from the patient or by proxy (first degree relative, spouse) if patients aren't in fully conscious status (eg.comatose, drowsiness, irritable).
Who cannot join
- Patients with chronic kidney disease (CKD) defined by baseline serum creatinine > 2.0 in male and 1.5 in female.
- Patients with End stage renal disease (ESRD) with or without renal replacement therapy.
- Patients with active cardiac disease : severe valvular heart, cardiomyopathy, decompensated heart failure NYHA II-IV, severe pulmonary hypertension.
- HIV/AIDs Patients.
- Allergy towards 0.9% NaCl or Ringer's Acetate.
- Any form of renal replacement therapy.
Show all 11Show fewer
- Intracranial bleeding within current hospitalization.
- Therapy with corticosteroid or non steroidal anti-inflammatory substance.
- Patients who predicted not to survive more than 24 hours.
- Pregnant and lactating patients.
- Withdrawal of active therapy.
Trial locations and contacts
1 site in 1 country.
About this study
The high chloride content of 0.9%sodium chloride (0.9%NaCl) leads to adverse pathophysiological effects in both animals and healthy human volunteers. Small randomized trials confirm that the hyperchloremic acidosis induced by 0.9%NaCl also occurs in patients. A strong signal is emerging from recent large propensity-matched and cohort studies for the adverse effects that 0.9% NaCl has on the clinical outcome in surgical and critically ill patients when compared with balanced crystalloids. Major complications are the increased incidences of acute kidney injury and the need for renal replacement therapy, and that pathological hyperchloremia may increase postoperative mortality.
Fluid resuscitation with 0.9% NaCl in animals with sepsis resulted in hyperchloremic metabolic acidosis, worsened AKI, and increased mortality when compared with resuscitation with a balanced crystalloid solution.
Read more
Furthermore, hyperchloremic acidosis also resulted in increased concentrations of circulating inflammatory mediators in an experimental model of severe sepsis in rats, with a dose-dependent increase in circulating interleukin-6, tumor necrosis factor-a, and interleukin-10 concentrations with increasing acidosis.
Thus, in this study, investigators compared the effects of a balanced crystalloid solution with 0.9% NaCl on the renal function in severe sepsis/septic shock patients. Investigators hypothesized that balanced crystalloid solution resuscitation would decrease AKI incidence and severity and would improve immunomodulatory effect when compared with 0.9% NaCl resuscitation.
- Conditions
- Sepsis, Septic Shock, Acute Kidney Injury
- Being tested
- Normal saline, Ringer's Acetate
- Medical subject headings
- Sepsis, Shock, Septic, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Normal salineDrug
for resuscitation in sepsis patients
Ringer's AcetateDrug
for resuscitation in sepsis patients
| Study group | Role | What they receive |
|---|---|---|
| normal saline | Active comparator | Not described Receives: Drug: Normal saline |
| balanced solution | Active comparator | Not described Receives: Drug: Ringer's Acetate |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of acute kidney injury for any stage and severity
Measured: at day 7
Secondary outcomes (9)
The neutrophil function (chemotaxis, CD11b ) between two randomized groups at
Measured: 0, 24, and 72 hours after resuscitation.
The monocyte function (HLA-DR) between two randomized groupsafter resuscitation.
Measured: at 0, 24, and 72 hours after resuscitation.
The inflammatory marker (IL-6, IL-10) between two randomized groups at
Measured: 0, 24, and 72 hours after resuscitation.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) after randomization and after resuscitation with trial fluid
Measured: at 0,24 and 72 hours after resuscitation.
Urinary liver-type fatty acid binding protein (L-FABP)
Measured: at 0,24 and 72 hours after resuscitation.
Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.
Measured: at 72 hours after randomization.
Need of renal replacement therapy within 72 hours after randomization
Measured: within 72 hours after randomization
Days alive without renal replacement therapy
Measured: in 28 days after randomization
Hospital length of stay for survivors sanctioned
Measured: at 28 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2017
- Study start1 Jul 2017
- Primary completion1 Jul 2018
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- More trials run by Chulalongkorn UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 116 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chulalongkorn University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nattachai Srisawat ,M.D., Chulalongkorn University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03277677
- Sponsor's protocol ID
- IRB.113/60
- Status last verified
- Mar 2021
- First submitted
- 7 Sep 2017
- Last updated
- 9 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Fluid Resuscitation With 0.9% Sodium Chloride Versus Balanced Crystalloid Solution on Renal Function of Sepsis Patients
- ClinicalTrials.gov ID
- NCT03277677
- Acronym / sponsor ID
- IRB.113/60
- Conditions
- Sepsis, Septic Shock, Acute Kidney Injury
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 116 participants (actual)
- Lead sponsor
- Chulalongkorn UniversityUniversity, hospital or other
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 1 Jul 2018 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 11 Sep 2017 (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.
The high chloride content of 0.9%sodium chloride (0.9%NaCl) leads to adverse pathophysiological effects in both animals and healthy human volunteers. Small randomized trials confirm that the hyperchloremic acidosis induced by 0.9%NaCl also occurs in patients. A strong signal is emerging from recent large propensity-matched and cohort studies for the adverse effects that 0.9% NaCl has on the clinical outcome in surgical and critically ill patients when compared with balanced crystalloids. Major complications are the increased incidences of acute kidney injury and the need for renal replacement therapy, and that pathological hyperchloremia may increase postoperative mortality.
Fluid resuscitation with 0.9% NaCl in animals with sepsis resulted in hyperchloremic metabolic acidosis, worsened AKI, and increased mortality when compared with resuscitation with a balanced crystalloid solution.
Furthermore, hyperchloremic acidosis also resulted in increased concentrations of circulating inflammatory mediators in an experimental model of severe sepsis in rats, with a dose-dependent increase in circulating interleukin-6, tumor necrosis factor-a, and interleukin-10 concentrations with increasing acidosis.
Thus, in this study, investigators compared the effects of a balanced crystalloid solution with 0.9% NaCl on the renal function in severe sepsis/septic shock patients. Investigators hypothesized that balanced crystalloid solution resuscitation would decrease AKI incidence and severity and would improve immunomodulatory effect when compared with 0.9% NaCl resuscitation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| normal saline | Active comparator | Drug: Normal saline |
| balanced solution | Active comparator | Drug: Ringer's Acetate |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Age ≥ 18 years old
- Who need fluid resuscitation in the Emergency Room (ER).
- Who have fulfilled the criteria for sepsis/septic shock within the previous 24 hours according to sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
- o Patients with infection and resulted from a host's systemic inflammatory response syndrome (SIRS) to infection are defined as sepsis if meet the criteria 2 or more of
- Patient who have Septic shock is a subset of sepsis in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality.
Key exclusion criteria (11 listed)
- Patients with chronic kidney disease (CKD) defined by baseline serum creatinine > 2.0 in male and 1.5 in female.
- Patients with End stage renal disease (ESRD) with or without renal replacement therapy.
- Patients with active cardiac disease : severe valvular heart, cardiomyopathy, decompensated heart failure NYHA II-IV, severe pulmonary hypertension.
- HIV/AIDs Patients.
- Allergy towards 0.9% NaCl or Ringer's Acetate.
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 |
|---|---|---|
| Normal salinefor resuscitation in sepsis patients | Drug | normal saline |
| Ringer's Acetatefor resuscitation in sepsis patients | Drug | balanced solution |
Primary outcome
The incidence of acute kidney injury for any stage and severity
Time frame: at day 7
9 secondary outcomes
The neutrophil function (chemotaxis, CD11b ) between two randomized groups at
Time frame: 0, 24, and 72 hours after resuscitation.
The monocyte function (HLA-DR) between two randomized groupsafter resuscitation.
Time frame: at 0, 24, and 72 hours after resuscitation.
The inflammatory marker (IL-6, IL-10) between two randomized groups at
Time frame: 0, 24, and 72 hours after resuscitation.
Urinary neutrophil gelatinase-associated lipocalin (NGAL) after randomization and after resuscitation with trial fluid
Time frame: at 0,24 and 72 hours after resuscitation.
Urinary liver-type fatty acid binding protein (L-FABP)
Time frame: at 0,24 and 72 hours after resuscitation.
Sequential [Sepsis-related] Organ Failure Assessment (SOFA) Score. (excluding Glasgow Coma Score) at 72 hours after randomization.
Time frame: at 72 hours after randomization.
Need of renal replacement therapy within 72 hours after randomization
Time frame: within 72 hours after randomization
Days alive without renal replacement therapy
Time frame: in 28 days after randomization
Hospital length of stay for survivors sanctioned
Time frame: at 28 days after randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2021.
- Individual participant dataSharing planned: No
Related trials for Sepsis
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
RecruitingPhase 4
A Study to Compare the Efficacy and Safety of Extended and Intermittent Infusion of Beta-lactams in Critically Ill Paediatric Patients
Infection, Sepsis
Not yet recruiting
Double Plasma Separation and Adsorption in Acute-on-Chronic Liver Failure (DPMAS-ACLF Trial)
Acute-on-Chronic Liver Failure (ACLF)
Active, not recruitingPhase 4
Thymosin Alpha 1 and IgM Levels in Sepsis
Sepsis, Septic Shock
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Normal saline and Ringer's Acetate in people with Sepsis and Septic Shock, run by Chulalongkorn University at 1 site in Thailand.
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 11 inclusion and 11 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: finished, as of the sponsor's last update on 9 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of acute kidney injury for any stage and severity (time frame: at day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 Mar 2021.