Protocolized Reduction of Non-resuscitation Fluids vs Usual Care in Septic Shock Feasibility Trial

Protocolized Reduction of Non-resuscitation Fluids Versus Usual Care in Septic Shock Patients: A Multicentre Feasibility Trial

The objectives of this feasibility trial are to assess the efficacy and feasibility of methods and procedures of a protocol purposed to compare a reduction of administration of non-resuscitation fluids to usual care in patients with septic shock.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital
  • Halmstad, Sweden
    • Halmstad Hospital
  • Helsingborg, Sweden
    • Helsingborg Hospital
  • Kristianstad, Sweden
    • Kristianstad Hospital
  • Lund, Sweden
    • Skåne University Hospital, Lund
  • Malmö, Sweden
    • Skåne University Hospital, Malmö
  • Uppsala, Sweden
    • Uppsala University Hospital
  • Östersund, Sweden
    • Östersund Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Adult (≥ 18 years of age)
• Septic shock according to the Sepsis 3 criteria: suspected or confirmed infection AND infusion of vasopressor/inotrope to maintain mean arterial pressure of 65 mmHg or above despite adequate fluid resuscitation AND lactate of 2 mmol/L or above at any time following ICU admission when there was a simultaneous need for vasopressor/inotrope.
• Inclusion within 12 hours after ICU admission.

Exclusion Criteria:

• Confirmed or suspected pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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 fluids are discontinued in participants with positive cumulative fluid balance who are not dehydrated; Intravenous fluid and enteral water are given as needed to correct electrolyte disturbances; Enteral nutrition with energy density of at least 2 kcal/ml is administered according to local practice; Starting 72 hours after inclusion, glucose at a concentration of at least 20% and a maximal dose of 1g/kg/day may be used as nutrition if enteral feeding is not tolerated. Glucose at this dose or lower may be started earlier in patients with insulin dependent diabetes if enteral feeding is not tolerated and local protocol mandates this; Parenteral nutrition is administered according to local protocol; Intravenous medications are concentrated according to a predefined protocol; Patients with neutral or negative cumulative fluid balance receive maintenance and other fluids such that 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) are given at a dose of 1 ml/kg/h unless local protocol states otherwise; Glucose is used at maximal concentration of 10% unless local protocol states otherwise.; Medications are concentrated according to local protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in fluid administration	Total difference in litres of administered fluids between groups	Within the first three days after inclusion (days 0-3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with sufficient clinical outcome data	Fraction of randomised patients with sufficient data for the following clinical outcomes: all-cause mortality, days alive and free of mechanical ventilation, acute kidney injury, and ischemic events in the ICU (cerebral, cardiac, intestinal or limb ischemia)	Within 90 days after inclusion
Proportion of participants assessed by EQ5D-5L and MoCA	Fraction of surviving randomized patients who were assessed by European Quality of Life-5 Dimensions 5- Level questionnaire (EQ5D-5L) and The Montreal Cognitive Assessment (MoCA)	6 months after inclusion
Inclusion of eligible patients	Fraction of all eligible patients who were randomised and consented	During inclusion
Protocol violations	Fraction of patients experiencing at least one protocol violation	Within 90 days after inclusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	All-cause mortality	90 days after inclusion
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 randomization until final discharge from ICU or death, whichever comes first, assessed up to 90 days
Days alive and free of mechanical ventilation	Days alive and free of mechanical ventilation	Within 90 days after inclusion
Cognitive function	Cognitive function measured using MoCA	6 months after inclusion
Health-Related Quality of Life	Health-Related Quality of Life measured using the EQ5D-5L questionnaire	6 months after inclusion
Total volume of non-resuscitation fluids administered	Total volume of non-resuscitation fluids administered	Within the first three days (days 0-3) and within the first five days (days 0-5) after inclusion
Renal function	Acute kidney injury stages according to Kidney Disease Improving Global Outcomes [KDIGO] criteria, urea, and days alive and free of renal replacement therapy [RRT]	Within 90 days after inclusion
Gastrointestinal function	Days alive with full enteral nutrition	Within 90 days after inclusion
Total volume of resuscitation fluids administered	Total volume of resuscitation fluids administered	Within the first three days (days 0-3) and within the first five days (days 0-5) after inclusion
Cumulative fluid balance	Cumulative fluid balance (excluding evaporation)	On day 3 and day 5 after inclusion
Diuretics administered	Daily dose and type of diuretics administered	Within the first five days (days 0-5) after inclusion
Hemodynamic stability	Daily highest dose of noradrenaline, daily lactate, and cardiovascular sequential organ failure assessment [SOFA] score	Within the first five days (days 0-5) after inclusion
Ischemic events	Number of patients with one or more ischemic events while in the ICU (cerebral, cardiac, intestinal or limb ischemia)	from randomization until final discharge from ICU or death, whichever comes first, assessed up to 90 days
GOSE score	Glasgow Outcome Scale Extended (GOSE) score	6 months after inclusion

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Linden A, Fisher J, Lilja G, Olsen MH, Sjovall F, Jungner M, Spangfors M, Samuelsson L, Oras J, Linder A, Unden J, Kander T, Lipcsey M, Nielsen N, Jakobsen JC, Bentzer P. Protocolised reduction of non-resuscitation fluids versus usual care in patients with septic shock (REDUSE): a protocol for a multicentre feasibility trial. BMJ Open. 2023 Feb 28;13(2):e065392. doi: 10.1136/bmjopen-2022-065392.

Helpful Links

• Markus Harboe Olsen, et al. Protocolised Reduction of Non-resuscitation Fluids Versus Usual Care in Septic Shock Patients (REDUSE) - a Statistical Analysis Plan for a Multicentre Feasibility Trial. 3.00, Zenodo, Dec. 2022, doi:10.5281/zenodo.7392132.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): September 13, 2022
• Study Completion (Actual): March 27, 2023

Study Registration Dates

• First Submitted: February 8, 2022
• First Submitted That Met QC Criteria: February 18, 2022
• First Posted (Actual): February 21, 2022

Study Record Updates

• Last Update Posted (Estimated): December 11, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Shock, Septic; Shock
• Other Study ID Numbers: REDUSE feasibility trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Beginning 9 months 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