Critically IllRESPONSENCT02860572
Non-interventional Follow-up Versus Fluid Bolus in RESPONSE to Oliguria in the Critically Ill
A study testing follow-up without intervention and fluid bolus in people with Critically Ill and Acute Kidney Injury, run by Helsinki University Central Hospital at 2 sites in Finland.
Trial summary
Background: After hypotension, oliguria (urine output less than 0.5 mL/kg/h) was the most common trigger to administer fluid bolus in a multinational practice survey in intensive care. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Critically Ill, Acute Kidney Injury, Sepsis
- What is being tested?
- follow-up without intervention and fluid bolus
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 2 sitesFinland
- Study dates
- 10 Jan 2017to 10 Dec 2020
- Phase
- Interventional
- 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 over 18
- Emergency admission to an ICU
- Mean arterial pressure (MAP) >65 mmHg (with vasopressors if needed) and initial fluid resuscitation for shock/hypovolemia has been given
- Oliguria (urine output less than 0.5mL/kg/h) for at least 2 consecutive hours
Who cannot join
- Marked fluctuations in hemodynamics within last 2 hours (cardiac arrhythmias, increase in norepinephrine need over 0.2ug/kg/min, need for initiation of inotrope/inodilator)
- Administration of furosemide within last 6 hours
- Chronic kidney disease (estimated pre-critical illness GFR < 60ml/min/1.73m2)
- Renal replacement therapy
- Among patients with acute kidney injury, urgent indications for commencing renal replacement therapy
- Fluid overload (cumulative fluid accumulation exceeds 10% of baseline body weight)
Show all 12Show fewer
- Pulmonary edema (bilateral infiltrates in chest x-ray)
- Active bleeding (need for transfusion, platelets, or fresh frozen plasma)
- Suspected or known intra-abdominal hypertension (IAP >16mmHg)
- Pregnant or lactating
- Expected survival less than 24h
- Obtaining informed consent is not possible/consent is denied
Trial locations and contacts
2 sites in 1 country.
Finland2 sites
Helsinki University Hospital, Meilahti
Helsinki, Uusimaa, 00290
Central Finland Central Hospital
Jyväskylä
About this study
Official title: Non-interventional Follow-up Versus Fluid Bolus in RESPONSE to Oliguria in the Optimization Phase of Fluid Therapy in the Critically Ill (the RESPONSE Trial)
Background: After hypotension, oliguria (urine output less than 0.5 mL/kg/h) was the most common trigger to administer fluid bolus in a multinational practice survey in intensive care. The effect of fluid bolus on cardiovascular variables can be very short-lived among patients in shock suggesting that fluid boluses in the optimization phase are unlikely to improve patient-centered outcomes. Moreover, a growing body of evidence suggests a poor renal response to fluid bolus.
Objective: To investigate, whether fluid bolus - as a standard of care - improves urine output in oliguric patients compared to a non-interventional follow-up approach without fluid bolus.
Read more
Design: Investigator-initiated, open, randomized, controlled study
Interventions:
- Intervention group - follow-up without intervention
- Control group - fluid bolus (500mL of balanced crystalloid over 30 minutes)
Randomization: 1:1 stratified according to the site, presence of acute kidney injury, and sepsis
Trial size: 130 patients randomized in 2 ICUs
Read the detailed description
Study hypothesis:
The investigators hypothesize that fluid bolus given due to oliguria does not improve urine output in a majority of patients, especially among those with acute kidney injury. Another study hypothesis is that patients receiving fluid bolus will have higher levels of endothelial damage biomarkers.
Intervention description:
Intervention group -follow-up without intervention; No intervention to increase the urine output within 2 hours will be done.
Standard group - Fluid bolus group: Patient will receive 500mL of balanced crystalloid intravenously over 30 minutes.
In both groups, if severe hemodynamic instability occurs, a rescue bolus of 500mL over 30 minutes may be given according to the decision of the treating clinician.
In both groups, all other ongoing infusions (nutrition and on-going clear fluids) will be held constant during the 2-hour period. Vasoactive medications, sedation, short-acting insulin, and other medications can be modified according the clinical need. No diuretics during the 2-hour study period are allowed. After two hours from randomization, treating clinician can modify the fluid and drug therapy according to the clinical needs of the patient. All administered fluids will be recorded 6 h from randomization.
Except for the study intervention period of 2 hours, no attempt to control fluid therapy will be done. During the study period, all other aspects of critical care will follow the ICU's standard operating procedures and clinician's prescription.
- Conditions
- Critically Ill, Acute Kidney Injury, Sepsis, Oliguria
- Being tested
- follow-up without intervention, fluid bolus
- Keywords
- fluid therapy, oliguria, endothelial injury
- Medical subject headings
- Critical Illness, Acute Kidney Injury, Sepsis, Oliguria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
follow-up without interventionOther
fluid bolusOther
| Study group | Role | What they receive |
|---|---|---|
| follow-up without intervention | Experimental | No intervention to increase the urine output within 2 hours will be done. Receives: Other: follow-up without intervention |
| Standard group - fluid bolus | Active comparator | Patient will receive 500mL of balanced crystalloid intravenously over 30 minutes. Receives: Other: fluid bolus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in individual mean cumulative urine output (mL/kg/h)
Doubling of the urine output is defined as clinically meaningful response
Measured: 2 hours after randomization compared to urine output 2 hours preceding randomization
Secondary outcomes (3)
The difference between groups in the change in individual urine output
Measured: 2 hours after randomization compared to urine output 2 hours preceding randomization
Duration of consecutive oliguria (urine output <0.5 mL/kg)
Measured: during ICU stay, i.e. as long as urine output stays below 0.5 mL/kg/h while the patient is in the ICU (an average of 5 to 7 days) or until renal replacement therapy is commenced
Cumulative fluid balance
Measured: six hours from randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2016 (estimated)
- Study start10 Jan 2017
- Primary completion10 Dec 2020
- Study completion10 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Critically IllStudies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Central Finland Hospital District
- Responsible party
- Principal investigator, Suvi Vaara, Helsinki University Central Hospital
- Investigators
- Suvi Vaara, MD, PhD, Principal investigator, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02860572
- Sponsor's protocol ID
- 200/13/03/02/16
- Acronym
- RESPONSE
- Status last verified
- Dec 2020
- First submitted
- 1 Aug 2016
- Last updated
- 14 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Publications
Serlo M, Inkinen N, Lakkisto P, Valkonen M, Pulkkinen A, Selander T, Pettila V, Vaara ST. Fluid bolus increases plasma hyaluronan concentration compared to follow-up strategy without a bolus in oliguric intensive care unit patients. Sci Rep. 2024 Sep 6;14(1):20808. doi: 10.1038/s41598-024-71670-2.
PubMed 39242877Inkinen N, Pettila V, Valkonen M, Serlo M, Backlund M, Hastbacka J, Pulkkinen A, Selander T, Vaara ST. Non-interventional follow-up versus fluid bolus in RESPONSE to oliguria in hemodynamically stable critically ill patients: a randomized controlled pilot trial. Crit Care. 2022 Dec 22;26(1):401. doi: 10.1186/s13054-022-04283-8.
PubMed 36550559Inkinen N, Selander T, Pettila V, Valkonen M, Backlund M, Wennervirta J, Pulkkinen A, Hastbacka J, Vaara ST. Noninterventional follow-up vs fluid bolus in RESPONSE to oliguria-The RESPONSE trial protocol and statistical analysis plan. Acta Anaesthesiol Scand. 2020 Sep;64(8):1210-1217. doi: 10.1111/aas.13599. Epub 2020 Apr 28.
PubMed 32270496
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-interventional Follow-up Versus Fluid Bolus in RESPONSE to Oliguria in the Optimization Phase of Fluid Therapy in the Critically Ill (the RESPONSE Trial)
- ClinicalTrials.gov ID
- NCT02860572
- Acronym / sponsor ID
- RESPONSE / 200/13/03/02/16
- Conditions
- Critically Ill, Acute Kidney Injury, Sepsis, Oliguria
- Keywords
- fluid therapy, oliguria, endothelial injury
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- Central Finland Hospital District
- Study start
- 10 Jan 2017 (actual)
- Primary completion
- 10 Dec 2020 (actual)
- Study completion
- 10 Dec 2020 (actual)
- First posted
- 9 Aug 2016 (estimated)
- 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.
Background: After hypotension, oliguria (urine output less than 0.5 mL/kg/h) was the most common trigger to administer fluid bolus in a multinational practice survey in intensive care. The effect of fluid bolus on cardiovascular variables can be very short-lived among patients in shock suggesting that fluid boluses in the optimization phase are unlikely to improve patient-centered outcomes. Moreover, a growing body of evidence suggests a poor renal response to fluid bolus.
Objective: To investigate, whether fluid bolus - as a standard of care - improves urine output in oliguric patients compared to a non-interventional follow-up approach without fluid bolus.
Design: Investigator-initiated, open, randomized, controlled study
Interventions:
- Intervention group - follow-up without intervention
- Control group - fluid bolus (500mL of balanced crystalloid over 30 minutes)
Randomization: 1:1 stratified according to the site, presence of acute kidney injury, and sepsis
Trial size: 130 patients randomized in 2 ICUs
Detailed description
Study hypothesis:
The investigators hypothesize that fluid bolus given due to oliguria does not improve urine output in a majority of patients, especially among those with acute kidney injury. Another study hypothesis is that patients receiving fluid bolus will have higher levels of endothelial damage biomarkers.
Intervention description:
Intervention group -follow-up without intervention; No intervention to increase the urine output within 2 hours will be done.
Standard group - Fluid bolus group: Patient will receive 500mL of balanced crystalloid intravenously over 30 minutes.
In both groups, if severe hemodynamic instability occurs, a rescue bolus of 500mL over 30 minutes may be given according to the decision of the treating clinician.
In both groups, all other ongoing infusions (nutrition and on-going clear fluids) will be held constant during the 2-hour period. Vasoactive medications, sedation, short-acting insulin, and other medications can be modified according the clinical need. No diuretics during the 2-hour study period are allowed. After two hours from randomization, treating clinician can modify the fluid and drug therapy according to the clinical needs of the patient. All administered fluids will be recorded 6 h from randomization.
Except for the study intervention period of 2 hours, no attempt to control fluid therapy will be done. During the study period, all other aspects of critical care will follow the ICU's standard operating procedures and clinician's prescription.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| follow-up without intervention | Experimental | Other: follow-up without interventionNo intervention to increase the urine output within 2 hours will be done. |
| Standard group - fluid bolus | Active comparator | Other: fluid bolusPatient will receive 500mL of balanced crystalloid intravenously over 30 minutes. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age over 18
- Emergency admission to an ICU
- Mean arterial pressure (MAP) >65 mmHg (with vasopressors if needed) and initial fluid resuscitation for shock/hypovolemia has been given
- Oliguria (urine output less than 0.5mL/kg/h) for at least 2 consecutive hours
Key exclusion criteria (12 listed)
- Marked fluctuations in hemodynamics within last 2 hours (cardiac arrhythmias, increase in norepinephrine need over 0.2ug/kg/min, need for initiation of inotrope/inodilator)
- Administration of furosemide within last 6 hours
- Chronic kidney disease (estimated pre-critical illness GFR < 60ml/min/1.73m2)
- Renal replacement therapy
- Among patients with acute kidney injury, urgent indications for commencing 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 |
|---|---|---|
| follow-up without intervention | Other | follow-up without intervention |
| fluid bolus | Other | Standard group - fluid bolus |
Primary outcome
Change in individual mean cumulative urine output (mL/kg/h)
Time frame: 2 hours after randomization compared to urine output 2 hours preceding randomization
Doubling of the urine output is defined as clinically meaningful response
3 secondary outcomes
The difference between groups in the change in individual urine output
Time frame: 2 hours after randomization compared to urine output 2 hours preceding randomization
Duration of consecutive oliguria (urine output <0.5 mL/kg)
Time frame: during ICU stay, i.e. as long as urine output stays below 0.5 mL/kg/h while the patient is in the ICU (an average of 5 to 7 days) or until renal replacement therapy is commenced
Cumulative fluid balance
Time frame: six hours from 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 14 Dec 2020.
- Derived from this study: PubMed 39242877Serlo M, Inkinen N, Lakkisto P, Valkonen M, Pulkkinen A, Selander T, Pettila V, Vaara ST. Fluid bolus increases plasma hyaluronan concentration compared to follow-up strategy without a bolus in oliguric intensive care unit patients. Sci Rep. 2024 Sep 6;14(1):20808. doi: 10.1038/s41598-024-71670-2.
- Derived from this study: PubMed 36550559Inkinen N, Pettila V, Valkonen M, Serlo M, Backlund M, Hastbacka J, Pulkkinen A, Selander T, Vaara ST. Non-interventional follow-up versus fluid bolus in RESPONSE to oliguria in hemodynamically stable critically ill patients: a randomized controlled pilot trial. Crit Care. 2022 Dec 22;26(1):401. doi: 10.1186/s13054-022-04283-8.
- Derived from this study: PubMed 32270496Inkinen N, Selander T, Pettila V, Valkonen M, Backlund M, Wennervirta J, Pulkkinen A, Hastbacka J, Vaara ST. Noninterventional follow-up vs fluid bolus in RESPONSE to oliguria-The RESPONSE trial protocol and statistical analysis plan. Acta Anaesthesiol Scand. 2020 Sep;64(8):1210-1217. doi: 10.1111/aas.13599. Epub 2020 Apr 28.
- Individual participant dataSharing planned: Yes
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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. This study is not recruiting at the moment.
Suvi Vaara, MD, PhD principal investigator
Helsinki University Central Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing follow-up without intervention and fluid bolus in people with Critically Ill and Acute Kidney Injury, run by Helsinki University Central Hospital at 2 sites in Finland.
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 12 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 14 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Finland. 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.
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?
Change in individual mean cumulative urine output (mL/kg/h) (time frame: 2 hours after randomization compared to urine output 2 hours preceding randomization). 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 NCT02860572, which also lists 3 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 14 Dec 2020.