GODIF: Goal-directed fluid removal with furosemide in intensive care patients

Background

Each year, more than 170,000 Australians are treated in intensive care units, where nearly all receive intravenous fluids to maintain their blood pressure and circulatory stability. However, when not carefully managed, this treatment can result in fluid overload, a condition linked to multi-organ failure and a higher risk of death. Studies show that for every extra millilitre per kilogram of fluid given, the risk of mortality rises by 2%. Despite the widespread use and potential serious consequences of fluid therapy, there is a major gap in evidence to guide when and how best to remove excess fluid.

Fluid overload remains a complex and often overlooked issue in Australian ICUs, with research indicating that patients frequently maintain a positive fluid balance during the early days of intensive care, which correlates with higher hospital mortality. International findings highlight the global impact of this problem, yet no randomised trials have tested fluid removal strategies in general ICU settings. The GODIF trial, currently underway in multiple European nations, seeks to address this evidence gap. Involving Australian centres in this global study is crucial to ensure locally applicable evidence and improve outcomes for critically ill Australians. High-quality research is urgently needed to establish effective de-resuscitation approaches and reduce long-term harm.

Aim

The primary objective of this trial is to evaluate whether goal-directed fluid removal using furosemide (a diuretic) improves outcomes in critically ill patients by increasing days alive and free of organ support. Through a large, multi-centre randomised clinical trial, this study aims to generate definitive evidence on a common yet poorly managed aspect of intensive care—fluid overload. If successful, the intervention has the potential to significantly improve survival and long-term functional outcomes, while reducing ICU stays and associated healthcare costs. Given that furosemide is inexpensive, and widely available, positive trial results could be rapidly adopted into clinical practice globally.

Research Methodology

The GODIF trial is an international, multi-centre, randomised, placebo-controlled, double-blinded clinical trial assessing the benefits and harms of goal-directed fluid removal using furosemide versus placebo in adult ICU patients with ≥5% fluid overload. The trial aims to determine whether this intervention improves patient-important outcomes, particularly days alive and out of hospital at 90 days. Participants are randomised 1:1 via a centralised web system, stratified by site, acute kidney injury status, and mortality risk. The study drug is administered via bolus and titrated infusion, guided by a fluid removal protocol. Recruitment in Australia will occur across 4 major ICUs, aiming to enrol approximately 100 patients over 12–18 months.

The primary outcome is days alive and out of hospital at 90 days, with secondary outcomes including mortality, organ support-free days, adverse events, health-related quality of life, and cognitive function at one year. The trial follows GCP standards and includes a Data Monitoring Committee, interim analyses, and detailed safety protocols. Australian coordination is led by The George Institute for Global Health, with trial completion and result dissemination expected by December 2027.

Current Status

Actively recruiting