Goal directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A trial protocol for a randomised, blinded trial (GODIF trial)

Abstract

Background: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of goal directed fluid removal with furosemide versus placebo in ICU patients with fluid overload.Methods: An investigator-initiated, international, randomised, stratified, blinded, parallel-group trial allocating 1000 adult ICU patients with fluid overload to infusion of furosemide versus placebo. The goal is to achieve a neutral fluid balance. The primary outcome is days alive and out of hospital 90 days after randomisation. Secondary outcomes are all-cause mortality at day 90 and 1-year after randomisation; days alive at day 90 without life support; number of participants with one or more serious adverse events or reactions; health-related quality of life and cognitive function at 1-year follow-up. A sample size of 1000 participants is required to detect an improvement of 8% in days alive and out of hospital 90 days after randomisation with a power of 90% and a risk of type 1 error of 5%. The conclusion of the trial will be based on the point estimate and 95% confidence interval; dichotomisation will not be used. ClinicalTrials. gov identifier: NCT04180397.

Goal‐directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A randomised, blinded trial (GODIF trial—First version)

“…A combination of the three parameters might be more precise compared to one parameter alone. We therefore updated the GODIF protocol accordingly and now recruit into the second version of the GODIF trial 20 . Until 22 November 2022, 182 participants have been included at 15 active trial sites in Denmark, Norway, and Finland.…”

“…The protocol for the GODIF trial was revised and on 1 June 2021 the second version of the GODIF trial was launched according to our adjusted protocol 20 . For this protocol, we developed a more pragmatic way of assessing fluid overload and neutral fluid balance.…”

“…We were unable to provide precise estimates of the benefits and harms of furosemide versus placebo in adult ICU patients with fluid overload because only 4.1% of the planned sample size was enrolled due to our early termination of the trial. We learned very important lessons which have resulted in changes in trial design, so the GODIF trial is now enrolling under an updated, second version of the protocol 20 …”

“…We learned very important lessons which have resulted in changes in trial design, so the GODIF trial is now enrolling under an updated, second version of the protocol. 20…”

Furosemide versus placebo for fluid overload in intensive care patients—The randomised GODIF trial second version: Statistical analysis plan

“…4 Here, we present the detailed statistical analysis plan of the todate largest and ongoing RCT of furosemide versus placebo in stable adult ICU patients with moderate to severe fluid overload (the GODIF trial second version). 6 This statistical analysis plan is published before finalising patient enrolment to increase transparency, prevent selective outcome reporting and data-driven analyses following the International Conference on Harmonisation (ICH) of Good Clinical Practice (GCP) guidelines. 7…”