Clinical trial NCT04931485: Protocolised Early De-Resuscitation in Septic Shock (REDUCE)
Official title: Protocolised Early De-Resuscitation in Septic Shock (REDUCE) - a Randomised Controlled Multi-centre Feasibility Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Septic Shock
Keywords: Septic shock
Fluid resuscitation
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
First posted: 2021-06-18
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be randomized to receive either fluid resuscitation/de-resuscitation according to the REDUCE protocol or standard of care.
Primary purpose: OTHER

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patient with a negative fluid balance on day 3
timeFrame: Up to day 3 after ICU admission
Secondary outcomes:
measure: Number of patients with fluid overload at day 3 and ICU discharge
timeFrame: From hospital admission to the end of ICU stay, on average after 7 days
measure: Feasibility of the REDUCE fluid protocol
timeFrame: From randomisation until the end of ICU stay, on average after 7 days
measure: Incidence of ischemic events and severe AKI
timeFrame: 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)
measure: Ventilator-free days at day 30
timeFrame: Up to 30 days after randomisation
measure: Vasopressor-free days at day 30
timeFrame: Up to 30 days after randomisation
measure: Renal replacement therapy
timeFrame: Up to 90 days after randomisation
measure: Number of patients with need for renal replacement at 90days
timeFrame: Up to 90 days after randomisation
measure: All-cause mortality
timeFrame: Up to 90 days after randomisation
Other outcomes:
measure: Daily cumulative fluid balance up to day 7
timeFrame: Throughout the ICU stay, on average 7 days
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Bern
country: Switzerland
facility: University Hospital Bern, Inselspital
city: St. Gallen
country: Switzerland
facility: Cantonal Hospital St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
Study officials:
affiliation: Department of Intensive Care, Inselspital, Bern University Hospital, Bern, Switzerland
name: Anna S Messmer, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.