Protocolised Early De-Resuscitation in Septic Shock (REDUCE) (REDUCE)

Protocolised Early De-Resuscitation in Septic Shock (REDUCE) - a Randomised Controlled Multi-centre Feasibility Study

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.

Study Overview

• Status: Completed
• Conditions: Septic Shock
• Intervention / Treatment: Other: Fluid management according to the REDUCE Fluid Protocol; Other: Standard of care

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel
  • Bern, Switzerland, 3010
    • University Hospital Bern, Inselspital
  • Sankt Gallen, Switzerland, 9000
    • Cantonal Hospital St. Gallen
  • Winterthur, Switzerland, 8400
    • Kantonsspital Winterthur

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention: REDUCE Protocol; Fluid resuscitation and de-resuscitation is based on the REDUCE fluid management protocol.	Other: Fluid management according to the REDUCE Fluid Protocol; Fluid management according to the protocol will be guided by pre-defined clinical signs for impaired perfusion and fluid overload.; Other Names: REDUCE protocol
Active Comparator: Standard of Care; Fluid resuscitation and de-resuscitation according to the standard of care	Other: Standard of care; Fluid resuscitation and de-resuscitation will be managed according to the standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patients with fluid overload at day 3 and ICU discharge	Fluid overload as defined as ((input-output)/admission weight)*100	From hospital admission to the end of ICU stay, on average after 7 days
Feasibility of the REDUCE fluid protocol	Number of REDUCE fluid protocol violations	From randomisation until the end of ICU stay, on average after 7 days
Incidence of ischemic events and severe AKI	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	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	Ventilator free days up to day 30	Up to 30 days after randomisation
Vasopressor-free days at day 30	Vasopressor free days up to day 30	Up to 30 days after randomisation
Renal replacement therapy	Need for and time on renal replacement therapy	Up to 90 days after randomisation
Number of patients with need for renal replacement at 90days	Number of patients with on-going need for renal replacement at 90days	Up to 90 days after randomisation
All-cause mortality	At 30days and 90 days after randomization	Up to 90 days after randomisation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Daily cumulative fluid balance up to day 7	Cumulative fluid balance is total input - total output	Throughout the ICU stay, on average 7 days

Collaborators and Investigators

• Sponsor: Insel Gruppe AG, University Hospital Bern
• Investigators: Principal Investigator: Anna S Messmer, MD, Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2021
• Primary Completion (Actual): February 10, 2025
• Study Completion (Actual): May 7, 2025

Study Registration Dates

• First Submitted: May 14, 2021
• First Submitted That Met QC Criteria: June 17, 2021
• First Posted (Actual): June 18, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Septic shock; Fluid resuscitation
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic; Health Services Administration; Health Care Quality, Access, and Evaluation; Quality of Health Care; Quality Indicators, Health Care; Standard of Care
• Other Study ID Numbers: REDUCE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No