Protocolized Reduction of Non-resuscitation Fluids Versus Usual Care in Septic Shock Patients (REDUSE)

The objective of this trial is to assess the beneficial and harmful effects of a restrictive strategy for administration of non-resuscitation fluids in adult patients with septic shock.

Study Overview

• Status: Recruiting
• Conditions: Septic Shock
• Intervention / Treatment: Other: Protocolised reduction of non-resuscitation fluids; Other: Usual care

• Study Type: Interventional
• Enrollment (Estimated): 1850
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Peter Bentzer; Phone Number: +46 42-4061111; Email: Peter.Bentzer@med.lu.se
• Study Contact Backup: Name: Jane Fisher; Email: jane.fisher@advansci-research.com

Study Locations

• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki university hospital
  • Kuopio, Finland
    • Not yet recruiting
    • Kuopio University Hospital
  • Tampere, Finland
    • Not yet recruiting
    • Tampere University Hospital
  • Turku, Finland
    • Not yet recruiting
    • Turku University Hospital
• Sweden
  • Danderyd, Sweden
    • Recruiting
    • Danderyd Hospital
  • Eskilstuna, Sweden
    • Recruiting
    • Malar Hospital
  • Falun, Sweden
    • Recruiting
    • Falun Hospital
  • Gothenburg, Sweden
    • Recruiting
    • Sahlgrenska University Hospital
  • Gothenburg, Sweden
    • Recruiting
    • Östra Hospital
  • Halmstad, Sweden
    • Recruiting
    • Halmstad Hospital
  • Helsingborg, Sweden
    • Recruiting
    • Helsingborg Hospital
  • Lund, Sweden
    • Recruiting
    • Skåne University Hospital, Lund
  • Malmo, Sweden
    • Recruiting
    • Skåne University Hospital, Malmö
  • Norrtälje, Sweden
    • Recruiting
    • Norrtälje Hospital
  • Stockholm, Sweden
    • Recruiting
    • Stockholm South General Hospital (SÖS)
  • Södertälje, Sweden
    • Not yet recruiting
    • Södertälje Hospital
  • Umeå, Sweden
    • Recruiting
    • University Hospital of Umeå
  • Uppsala, Sweden
    • Recruiting
    • Uppsala University Hospital
  • Varberg, Sweden
    • Recruiting
    • Varberg Hospital
  • Örebro, Sweden
    • Recruiting
    • Örebro University Hospital
  • Östersund, Sweden
    • Recruiting
    • Östersund Hospital
• United Kingdom
  • Cardiff, United Kingdom
    • Not yet recruiting
    • University Hospital of Wales

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (≥ 18 years of age)
• Septic shock according to the Sepsis 3 criteria at any time within 12 hours after ICU admission (suspected or confirmed infection, plasma lactate above 2 mmol/L, and infusion of vasopressor/inotrope to maintain mean arterial pressure of 65mmHg or above after receiving adequate fluid resuscitation [> 1L within 12 h of screening]) and need for vasopressors at the time of screening.

Exclusion Criteria:

• Confirmed or suspected pregnancy
• Previous inclusion in the trial
• Screened more than 12 hours after ICU admission

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Protocolised reduction of non-resuscitation fluids; Participants receive non-resuscitation fluids according to a pre-defined protocol starting within two hours of randomization. The intervention is continued for the duration of the ICU admission up to a maximum of 90 days.	Other: Protocolised reduction of non-resuscitation fluids; Maintenance fluid: discontinued if cumulative fluid balance is positive and patient is not dehydrated Intravenous fluid and enteral water: as needed to correct electrolyte disturbances Enteral nutrition (at least 2 kcal/ml): per local practice Glucose (conc. ≥20%, dose ≤1g/kg/day): may be used as nutrition if enteral feeding not tolerated starting 72h after inclusion. May be started earlier in patients with insulin-dependent diabetes or risk of hypoglycemia per local practice Parenteral nutrition: per local practice Intravenous medications: concentrated according to a predefined protocol Patients with neutral or negative cumulative fluid balance receive maintenance and other fluids so the total dose of fluids covers the daily need of water (about 1ml/kg/h)
Other: Usual Care; Participants receive non-resuscitation fluids according to local routines.	Other: Usual care; Participants receive non-resuscitation fluids according to local routines, with the following stipulations: Maintenance fluids (crystalloids and/or glucose and/or enteral water): given at a dose of 1 ml/kg/h unless local protocol states otherwise Glucose: used at maximal concentration of 10% unless local protocol states otherwise. Medications: concentrated per local protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause mortality	90 days after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complications in the ICU	Number of patients with one or more of the following complications in the ICU: cerebral, cardiac, intestinal or limb ischemia, or any acute kidney injury.	From inclusion until final discharge from ICU or death, whichever comes first, assessed up to 90 days
Cognitive function	Cognitive function measured using the Montreal Cognitive Assessment (MoCA)	6 months after inclusion
Health-Related Quality of Life	Health-Related Quality of Life measured using the European Quality of Life visual analogue scale (EQ-VAS)	6 months after inclusion
Mechanical ventilation-free days	Mechanical ventilation-free days	Within 90 days after inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major adverse kidney events (MAKE)	The composite of death, new receipt of renal replacement therapy, or persistent renal dysfunction (defined as a final inpatient creatinine value ≥200% of the baseline value)	90 days after inclusion
Cumulative dose of diuretics	Cumulative dose of diuretics (defined daily doses according to the World Health Organization [WHO])	5 days after inclusion
Glasgow Outcome Scale Extended (GOSE) score	GOSE score	6 months after inclusion
Health-Related Quality of Life	Health-Related Quality of Life measured using the European Quality of Life visual 5-dimension 5-level scale (EQ-5D-5L) questionnaire	6 months after inclusion
Health and disability	Health and disability measured using the WHO Disability Assessment Schedule (WHODAS) 2.0 (12 item version)	6 months after inclusion
Modified Fatigue Impact Scale (MFIS)	MFIS questionnaire (full-length version)	6 months after inclusion
Mortality	All-cause mortality	12 months after inclusion
Hypernatremia	Number of patients with hypernatremia (sodium > 159 mmol/L)	From inclusion until final discharge from ICU or death, whichever comes first, assessed up to 90 days
Acid-base disturbances	Number of patients with acid-base disturbances (hyperchloremic acidosis [pH < 7.15 and plasma Cl- > 115] or metabolic alkalosis [pH > 7.59 and S-BE > 9])	From inclusion until final discharge from ICU or death, whichever comes first, assessed up to 90 days
Central venous catheter-related complications	Number of patients with any central venous catheter related complications that could potentially be related to concentrated drugs given in the intervention group (for example, thrombosis, stenosis, malfunction, and infections)	From inclusion until final discharge from ICU or death, whichever comes first, assessed up to 90 days
Number of days in the ICU	Number of days in the ICU	Within 90 days of inclusion
Hospital-free days	Hospital-free days	Within 90 days after inclusion
Vasopressor-free days	Vasopressor-free days	Within 90 days after inclusion
Renal replacement therapy (RRT)-free days	RRT-free days	Within 90 days after inclusion
Hypoglycaemia	Number of patients with moderate hypoglycaemia (glucose 3.9 - 2.3 mmol/l) and severe hypoglycaemia (glucose ≤ 2.2 mmol/l)	From inclusion until final discharge from ICU or death, whichever comes first, assessed up to 90 days

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Peter Bentzer, Region Skane

Publications and helpful links

General Publications

• Bentzer P, Linden A, Olsen MH, Lilja G, Fisher J, Sjovall F, Kander T, Lengquist M, Samuelsson L, Unden J, Palmnas E, Oras J, Cronhjort M, Balintescu A, Lind A, Ahlstrom B, Meirik M, Savilampi J, Pekkarinen P, Berggren A, Oscarsson N, Said M, Castegren M, Faria S, Hemberg L, Linder A, Lipcsey M, Skrifvars MB, Wise MP, Nielsen N, Jakobsen JC. Protocolized REDUction of Non-Resuscitation Fluids in SEptic Shock Patients. A Protocol for the REDUSE Randomized Clinical Trial. Acta Anaesthesiol Scand. 2025 Aug;69(7):e70095. doi: 10.1111/aas.70095.

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2023
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): July 1, 2028

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 18, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: septic shock
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Shock; Pathological Conditions, Signs and Symptoms; Shock, Septic
• Other Study ID Numbers: REDUSE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Approximately one year after publication of the main report of this trial individual de-identified data will be available for sharing with researchers who provide a methodologically sound proposal as judged by the steering committee. To gain access, data requestors will need to sign a data access agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No