Protocolised Early De-Resuscitation in Septic Shock (REDUCE)

Septic Shock Clinical Trial

— REDUCE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04931485
• Other study ID #: REDUCE
• Status: Recruiting
• Phase: N/A
• Start date: July 19, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2024
• Source: Insel Gruppe AG, University Hospital Bern
• Contact: Anna S Messmer, MD
• Phone: +41316325300
• Email: anna.messmer[@]insel.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 170
• Est. completion date: December 31, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Septic Shock
• Shock
• Shock, Septic

Intervention

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

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel
Switzerland	University Hospital Bern, Inselspital	Bern
Switzerland	Cantonal Hospital St. Gallen	St. Gallen
Switzerland	Kantonsspital Winterthur	Winterthur

Sponsors (1)

Lead Sponsor	Collaborator
Insel Gruppe AG, University Hospital Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Daily cumulative fluid balance up to day 7	Cumulative fluid balance is total input - total output	Throughout the ICU stay, on average 7 days
Primary	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	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
Secondary	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
Secondary	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)
Secondary	Ventilator-free days at day 30	Ventilator free days up to day 30	Up to 30 days after randomisation
Secondary	Vasopressor-free days at day 30	Vasopressor free days up to day 30	Up to 30 days after randomisation
Secondary	Renal replacement therapy	Need for and time on renal replacement therapy	Up to 90 days after randomisation
Secondary	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
Secondary	All-cause mortality	At 30days and 90 days after randomization	Up to 90 days after randomisation