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)

Funding Information: SW has received a grant from Merchant Jakob Ehrenreich and wife Grete Ehrenreich's Foundation to production of trial drug for the GODIF trial. AP has received research funding from the Novo Nordisk Foundation, Health Insurance Denmark (Sygeforsikringen Danmark), Fresenius Kabi, Denmark, and Pfizer, Denmark. MO has received research funding from Fresenius Medical Care, Baxter and Biomerieux. MHB has received research funding for the GODIF trial from Novo Nordisk Foundation, Jakob Madsen's and wife Olga Madsen's Foundation, Svend Andersen's Foundation, and Health Insurance Denmark (Sygeforsikringen Danmark). No authors received any financial gain. All other authors declared no conflicts of interest. Publisher Copyright: © 2022 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.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. Perspective: The GODIF trial will provide important evidence of possible benefits and harms of fluid removal with furosemide in adult ICU patients with fluid overload.Peer reviewe

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

Publisher Copyright: © 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.Background: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. Methods: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. Conclusion: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. Trial Registrations: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.Peer reviewe

Kystbeskyttelse i Danmark - hvorfor og hvordan?

Der er stigende behov for kystbeskyttelse på grund af klimaforandringerne og stigende havniveau. Kystbeskyttelse kan imidlertid påvirke havnaturen og lokalt fiskeri negativt. Her forklarer vi, hvorfor det er nødvendigt at beskytte kysterne, hvordan man traditionelt gør det, og hvordan det måske er muligt både at beskytte kysten og gavne naturen