Efficacy and Safety of a Balanced Gelatine Solution for Fluid Resuscitation in Sepsis: A Prospective, Randomised, Controlled, Double-Blind Trial-GENIUS Trial

Abstract

Crystalloid; Fluid balance; Fluid resuscitation

Cristaloide; Balanç de fluids; Reanimació amb fluids

Cristaloide; Balance de líquidos; Reanimación con líquidos

Background/Objective: Sepsis is a leading cause of death in noncoronary intensive care units (ICUs). Fluids for intravascular resuscitation include crystalloids and colloids. There is extensive clinical evidence on colloid use, but large trials comparing gelatine with crystalloid regimens in ICU and septic patients are lacking. This study aimed to determine whether early, protocol-driven volume resuscitation using a gelatine-based regimen achieves hemodynamic stability (HDS) more rapidly than a crystalloid-based regimen in septic patients. Methods: This prospective, controlled, randomised, double-blind, multinational phase IV study compared two parallel groups of septic patients receiving a gelatine-based regimen (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG each, at a 1:1 ratio) or a crystalloid regimen (Sterofundin® ISO). Primary endpoint was time to first HDS within 48 h after randomisation. Secondary endpoints included fluid overload, fluid balance, and patient outcomes. Results: 167 patients were randomised. HDS was achieved after 4.7 h in the gelatine group and after 5.8 h in the crystalloid group (p = 0.3716). The gelatine group had a more favourable fluid balance at 24 h (medians: 3463.00 mL vs. 4164.00 mL; p = 0.0395) and less fluid overload (medians: 4296.05 vs. 5218.75%; p = 0.0217). No differences were observed in serious adverse events or mortality. Conclusions: The study provided clinical evidence of balanced gelatine solution for volume resuscitation in septic patients, although it was terminated prematurely. The early and protocol-based administration of gelatine was safe and effective in the enrolled patient population. Time to HDS was not different between groups but the gelatine-based regimen led to better fluid balance and less fluid overload.

In this clinical study, B. Braun Melsungen AG, Carl-Braun Str. 1, D-34212 Melsungen acts as the sponsor, funder, and data holder of this study. B. Braun Melsungen AG organised protocol development and contracted a contract research organisation (CRO) for clinical trial application, monitoring, and collection/analysis of study data. Investigational tests and reference products were produced and delivered by B. Braun Melsungen AG to all participating sites.