Furosemide in Early Acute Kidney Injury

• Status: Terminated
• Trial end date: 2014-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Acute renal failure, now referred to as acute kidney injury, is common in intensive care unit patients, contributes to high morbidity and mortality, and has no proven interventions with benefit once established. In addition to supportive care, these patients frequently receive diuretic therapy, most commonly furosemide.

Prior trials showed no impact of furosemide on clinical outcomes and perhaps harm, however, these trials suffered from numerous limitations and lack applicability to modern intensive care unit patients. As a result, there appears a disconnect between clinical practice and available evidence. Survey data supports the view of clinical equipoise for use of furosemide in intensive care unit patients with early acute kidney injury. Moreover, these data also confirm there is an urgent need for higher quality and more definitive evidence from randomized trial on furosemide use in early acute kidney injury.

Accordingly, the investigators propose to conduct a pilot phase II randomized, blinded, placebo-controlled trial comparing furosemide to placebo in ICU patients with early acute kidney injury.

The specific aims of this study are:

1. To compare the efficacy and safety of a continuous infusion of furosemide versus placebo titrated to the physiology parameter of urine output in early acute kidney injury on the primary outcome of progression in severity of kidney injury in intensive care unit patients with early AKI and stratified by the presence of sepsis.

2. To evaluate selected secondary endpoints on the impact of furosemide versus placebo, specifically: fluid balance goals; electrolyte and acid-base balance; the need for renal replacement therapy (i.e. dialysis); total duration of acute kidney injury; the rate of renal recovery; and mortality.

3. To compare the impact of furosemide versus placebo on the trajectory of serum and urinary biomarkers (neutrophil gelatinase-associated lipocalin [NGAL], interleukin-18 [IL-18]) and evaluate whether these biomarkers perform superior to conventional measures (creatinine, urea) for monitoring the progression of kidney injury and the prediction of outcome.

This trial represents part of a larger initiative aimed towards expanding our understanding of the treatment of acute kidney injury in intensive care unit patients and evaluating interventions that may potentially reduce kidney injury and improve clinical outcomes.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alberta
• Collaborators: Austin Hospital, Melbourne Australia; Princess Alexandra Hospital, Brisbane, Australia
• Treatments: Furosemide

Criteria

Inclusion Criteria:

• Informed and written consent by patient or surrogate

• Peripheral or central intravenous catheter

• The presence of early AKI

• 2 or more criteria for the systemic inflammatory response syndrome (SIRS) within 24 hours

• Achieved immediate resuscitation goals

Exclusion Criteria:

• Confirmed or suspected pregnancy

• Age <18 years

• Stage 4 or greater chronic kidney disease or kidney transplantation

• Acute pulmonary edema requiring urgent use of furosemide or RRT

• Patient is moribund with expected death within 24 hours

• Known or suspected drug allergy to furosemide

• Enrolled in concomitant randomized trial