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Open Access 01-12-2021 | Septicemia | Study protocol

Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial

GENIUS—Gelatine use in ICU and sepsis

Authors: Gernot Marx, Kai Zacharowski, Carole Ichai, Karim Asehnoune, Vladimír Černý, Rolf Dembinski, Ricard Ferrer Roca, Dietmar Fries, Zsolt Molnar, Peter Rosenberger, Manuel Sanchez-Sanchez, Tobias Schürholz, Tamara Dehnhardt, Sonja Schmier, Elke von Kleist, Ute Brauer, Tim-Philipp Simon

Published in: Trials | Issue 1/2021

Abstract

Background

Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime.

Methods

This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90.

Discussion

This study aims to generate evidence regarding which regimen—a gelatine-crystalloid regimen or a pure crystalloid regimen—is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload.

Trial registration

The European clinical trial database EudraCT 2015-000057-20 and the ClinicalTrials.gov Protocol Registration and Results System ClinicalTrials.gov NCT02715466. Registered on 17 March 2016.

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Title: Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial
GENIUS—Gelatine use in ICU and sepsis
Authors: Gernot Marx
Kai Zacharowski
Carole Ichai
Karim Asehnoune
Vladimír Černý
Rolf Dembinski
Ricard Ferrer Roca
Dietmar Fries
Zsolt Molnar
Peter Rosenberger
Manuel Sanchez-Sanchez
Tobias Schürholz
Tamara Dehnhardt
Sonja Schmier
Elke von Kleist
Ute Brauer
Tim-Philipp Simon
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Septicemia
Septicemia
Septic Shock
Volume Replacement
Published in: Trials / Issue 1/2021
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-021-05311-8

Keynote webinar | Spotlight on medication adherence

Springer Medicine

GENIUS—Gelatine use in ICU and sepsis

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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