Protocolised Early De-Resuscitation in Septic Shock (REDUCE)

NCT04931485 | Completed DMC

• 1 other identifier: REDUCE
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 4

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.

Conditions

Septic Shock

Keywords

Septic shock; Fluid resuscitation

Outcome Measures

Primary Outcomes (1)

• Proportion of patient with a negative fluid balance on day 3

  Proportion of patients with a negative cumulative fluid balance on day 3

  Up to day 3 after ICU admission

Secondary Outcomes (8)

• 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

• Feasibility of the REDUCE fluid protocol

  From randomisation until the end of ICU stay, on average after 7 days

• 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)

• Ventilator-free days at day 30

  Up to 30 days after randomisation

• Vasopressor-free days at day 30

  Up to 30 days after randomisation

Other Outcomes (1)

• Daily cumulative fluid balance up to day 7

  Throughout the ICU stay, on average 7 days

Study Arms (2)

Intervention: REDUCE Protocol

EXPERIMENTAL

Fluid resuscitation and de-resuscitation is based on the REDUCE fluid management protocol.

Other: Fluid management according to the REDUCE Fluid Protocol

Standard of Care

ACTIVE COMPARATOR

Fluid resuscitation and de-resuscitation according to the standard of care

Other: Standard of care

Interventions

Fluid management according to the REDUCE Fluid Protocol OTHER

Fluid management according to the protocol will be guided by pre-defined clinical signs for impaired perfusion and fluid overload.

Also known as: REDUCE protocol

Intervention: REDUCE Protocol

Standard of care OTHER

Fluid resuscitation and de-resuscitation will be managed according to the standard of care

Standard of Care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (4)

University Hospital Basel

Basel, 4031, Switzerland

Location

University Hospital Bern, Inselspital

Bern, 3010, Switzerland

Location

Cantonal Hospital St. Gallen

Sankt Gallen, 9000, Switzerland

Location

Kantonsspital Winterthur

Winterthur, 8400, Switzerland

Location

Related Publications (1)

• Messmer A, Pietsch U, Siegemund M, Buehler P, Waskowski J, Muller M, Uehlinger DE, Hollinger A, Filipovic M, Berger D, Schefold JC, Pfortmueller CA. Protocolised early de-resuscitation in septic shock (REDUCE): protocol for a randomised controlled multicentre feasibility trial. BMJ Open. 2023 Sep 21;13(9):e074847. doi: 10.1136/bmjopen-2023-074847.

  PMID: 37734896 BACKGROUND

MeSH Terms

Conditions

Shock, Septic

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Anna S Messmer, MD

  Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Outcome assessors will be blinded to the treatment allocation.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be randomized to receive either fluid resuscitation/de-resuscitation according to the REDUCE protocol or standard of care.

Study Record Dates

• First Submitted: May 14, 2021
• First Posted: June 18, 2021
• Study Start: July 19, 2021
• Primary Completion: February 10, 2025
• Study Completion: May 7, 2025
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CH (4)