Non-interventional Follow-up Versus Fluid Bolus in RESPONSE to Oliguria in the Critically Ill

Sepsis Clinical Trial

— RESPONSE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02860572
• Other study ID #: 200/13/03/02/16
• Status: Completed
• Phase: N/A
• Start date: January 10, 2017
• Est. completion date: December 10, 2020

Study information

• Verified date: December 2020
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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:

1. Intervention group - follow-up without intervention

2. 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: December 10, 2020
• Est. primary completion date: December 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

• 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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Critical Illness
• Critically Ill
• Oliguria
• Sepsis

Intervention

Other:
• follow-up without intervention

• fluid bolus

Locations

Country	Name	City	State
Finland	Helsinki University Hospital, Meilahti	Helsinki	Uusimaa
Finland	Central Finland Central Hospital	Jyväskylä

Sponsors (2)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Central Finland Central Hospital

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients receiving rescue boluses and the number of rescue boluses		study intervention period (i.e. 2 hours)
Other	Highest stage of acute kidney injury		within 24 hours, 48 hours and during ICU stay (an average of 5 to 7 days or up to 30 days if patient is still in ICU)
Other	Number of patients with one or several protocol violation(s) and number of those per patient		study intervention period (i.e. 2 hours)
Other	Number of patients with adverse events		from randomization to next morning
Other	Number of patients receiving renal replacement therapy		during ICU stay(an average of 5 to 7 days or up to 30 days if patient is still in ICU)
Other	change in mean arterial pressure		from randomization to 2 hours post-randomization
Other	change in heart rate		from randomization to 2 hours post-randomization
Primary	Change in individual mean cumulative urine output (mL/kg/h)	Doubling of the urine output is defined as clinically meaningful response	2 hours after randomization compared to urine output 2 hours preceding randomization
Secondary	The difference between groups in the change in individual urine output		2 hours after randomization compared to urine output 2 hours preceding randomization
Secondary	Duration of consecutive oliguria (urine output <0.5 mL/kg)		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
Secondary	Cumulative fluid balance		six hours from randomization