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
Details
Lead Sponsor:
University of Alberta
Collaborators:
Austin Hospital, Melbourne Australia Princess Alexandra Hospital, Brisbane, Australia