Protocolised Early De-Resuscitation in Septic Shock (REDUCE)
- Conditions
- Septic Shock
- Interventions
- Other: Standard of careOther: Fluid management according to the REDUCE Fluid Protocol
- Registration Number
- NCT04931485
- Lead Sponsor
- Insel Gruppe AG, University Hospital Bern
- Brief Summary
Background: Recent studies have questioned the safety of current fluid resuscitation strategies in patients with septic shock as prospective and observational data suggesting that the resulting fluid overload is associated with mortality. Two strategies have evolved to prevent or minimize fluid overload: restrictive fluid administration or active removal of accumulated fluid. While several small trials show benefits with a restrictive fluid administration regimen, active protocolized de-resuscitation was scarcely evaluated. The combination of both strategies yet warrants systematic evaluation.
Aim: This study aims to assess the efficacy and feasibility of an early active de-resuscitation protocol in patients with septic shock. We hypothesize that the application of a structured early de-resuscitation protocol versus standard of care will lead to less fluid overload at day three after ICU admission.
Study Intervention: Patients admitted to the ICU with confirmed or suspected septic shock (Sepsis-3 definition) will be randomized (1:1) to either the intervention or standard of care. In the intervention arm, patients are managed according to the REDUCE fluid management protocol during resuscitation and de-resuscitation.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 170
- Patients admitted to ICU with the diagnosis of septic shock as defined according to the Sepsis-3 criteria (suspected or confirmed infection AND vasopressor/inotrope ongoing to maintain MAP ≥ 65 mmHg AND Lactate ≥ 2 mmol/l in the last 6 hours
- Age <18 years
- Septic shock for more than 12 hours at the time of screening
- Acute burn injury >/= 10% of the body surface area
- Known pregnancy or lactating women
- Consent not obtainable due to national legislation
- Patients on chronic dialysis
- Patients that are known to be allergic to furosemide or metolazone
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard of Care Standard of care Fluid resuscitation and de-resuscitation according to the standard of care Intervention: REDUCE Protocol Fluid management according to the REDUCE Fluid Protocol Fluid resuscitation and de-resuscitation is based on the REDUCE fluid management protocol.
- Primary Outcome Measures
Name Time Method Proportion of patient with a negative fluid balance on day 3 Up to day 3 after ICU admission Proportion of patients with a negative cumulative fluid balance on day 3
- Secondary Outcome Measures
Name Time Method Vasopressor-free days at day 30 Up to 30 days after randomisation Vasopressor free days up to day 30
Ventilator-free days at day 30 Up to 30 days after randomisation Ventilator free days up to day 30
All-cause mortality Up to 90 days after randomisation At 30days and 90 days after randomization
Number of patients with fluid overload at day 3 and ICU discharge From hospital admission to the end of ICU stay, on average after 7 days Fluid overload as defined as ((input-output)/admission weight)\*100
Number of patients with need for renal replacement at 90days Up to 90 days after randomisation Number of patients with on-going need for renal replacement at 90days
Feasibility of the REDUCE fluid protocol From randomisation until the end of ICU stay, on average after 7 days Number of REDUCE fluid protocol violations
Incidence of ischemic events and severe AKI Ischemic events and AKI: From randomisation until the end of ICU stay (on average after 7 days), and at day 30; electrolyte and acid-base/medication associated safety endpoints: during ICU stay (on average 7 days) Number of patients with:ischaemic events, severe AKI (AKIN stage 2 or more); respectively episodes of: severe hypernatremia (sodium \>/= 155mmol/l), severe hypokalemia (\< 3.0 mmol/l), severe metabolic alkalosis (pH \>/= 7.55, bicarbonate \>/= 35 mmol/l), anaphylactic reaction to diuretic drug
Renal replacement therapy Up to 90 days after randomisation Need for and time on renal replacement therapy
Trial Locations
- Locations (4)
University Hospital Basel
🇨🇭Basel, Switzerland
University Hospital Bern, Inselspital
🇨🇭Bern, Switzerland
Cantonal Hospital St. Gallen
🇨🇭St. Gallen, Switzerland
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland