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

Abstract

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.

Keywords: crystalloid; fluid balance; fluid resuscitation; gelatine; sepsis.

Figure 1

Study flowchart. The CONSORT flowchart shows enrolment, randomisation, and follow-up. Patients were excluded if they ¹ prematurely discontinued the study treatment due to adverse events, ² completed the study from randomisation to Day 28 or ICU discharge, whichever occurred first, or ³ were transferred to the ICU of an external hospital or received emergency surgery due to the initial disease.

Figure 2

Box plot of time to haemodynamic stability (ITT). The length of the box represents the interquartile range (IQR). The horizontal line in the box interior represents the group median. The symbol in the box interior represents the group mean. The whiskers extend to 1.5 times the IQR above the upper quartile and below the lower quartile. Circles above whiskers represent outliers. (a) Box plot of the time to haemodynamic stability of all patients (ITT); (b) Predefined subgroup analysis of the primary efficacy endpoint in surgical patients: box plot of time to haemodynamic stability of surgical patients (ITT).

Figure 3

Line plot of creatinine clearance (CCr) over time (until Day 28/ICU discharge/study discontinuation) by treatment group. Furthermore, data from FU1 are shown. Mean values +/− standard errors are presented with dots and bars, respectively.