Furosemide in Early Acute Kidney Injury

NCT00978354 | Terminated Phase 2 DMC

• 1 other identifier: AHFMR-0920
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 4

Brief 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. 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. 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. 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.

Conditions

Acute Renal Failure

Keywords

acute kidney injury; acute renal failure; loop diuretic; critical illness; sepsis; renal replacement therapy; dialysis; renal recovery; survival

Outcome Measures

Primary Outcomes (1)

• Worsening AKI

  7 days

Secondary Outcomes (4)

• Fluid balance

  7 days

• Renal replacement therapy (RRT)

  7 days

• Renal Recovery

  90-days

• Survival

  90-days

Study Arms (2)

Furosemide

ACTIVE COMPARATOR

Furosemide intravenous continuous infusion

Drug: Furosemide

Normal Saline

PLACEBO COMPARATOR

Normal saline titrated continuous intravenous infusion

Drug: Normal Saline

Interventions

Furosemide DRUG

Continuous intravenous infusion of furosemide titrated to urine output

Also known as: Lasix

Furosemide

Normal Saline DRUG

Continuous intravenous infusion 0.9% normal saline placebo control

Also known as: 0.9% saline

Normal Saline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed and written consent by patient or surrogate
• Peripheral or central intravenous catheter
• The presence of early AKI
• or more criteria for the systemic inflammatory response syndrome (SIRS) within 24 hours
• Achieved immediate resuscitation goals

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead
• Austin Hospital, Melbourne Australia: collaborator
• Princess Alexandra Hospital, Brisbane, Australia: collaborator

Study Sites (4)

Princess Alexandra Hospital

Brisbane, Queensland, 4012, Australia

Location

Austin Hospital

Melbourne, Victoria, 3084, Australia

Location

General Systems Intensive Care Unit, University of Alberta

Edmonton, Alberta, T6G2B7, Canada

Location

University of Laval

Québec, Quebec, G1V 0A6, Canada

Location

Related Publications (3)

• Hashimoto H, Yamada H, Murata M, Watanabe N. Diuretics for preventing and treating acute kidney injury. Cochrane Database Syst Rev. 2025 Jan 29;1(1):CD014937. doi: 10.1002/14651858.CD014937.pub2.

  PMID: 39878152 DERIVED

• Bagshaw SM, Gibney RTN, Kruger P, Hassan I, McAlister FA, Bellomo R. The effect of low-dose furosemide in critically ill patients with early acute kidney injury: A pilot randomized blinded controlled trial (the SPARK study). J Crit Care. 2017 Dec;42:138-146. doi: 10.1016/j.jcrc.2017.07.030. Epub 2017 Jul 12.

  PMID: 28732314 DERIVED

• Bagshaw SM, Gibney RT, McAlister FA, Bellomo R. The SPARK Study: a phase II randomized blinded controlled trial of the effect of furosemide in critically ill patients with early acute kidney injury. Trials. 2010 May 11;11:50. doi: 10.1186/1745-6215-11-50.

  PMID: 20459801 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury; Critical Illness; Sepsis

Interventions

Furosemide; Saline Solution

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Infections; Systemic Inflammatory Response Syndrome; Inflammation

Intervention Hierarchy (Ancestors)

Sulfanilamides; Sulfonamides; Amides; Organic Chemicals; Aniline Compounds; Amines; Sulfones; Sulfur Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sean M Bagshaw, MD MSc

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 16, 2009
• Study Start: September 1, 2009
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: September 30, 2015

Record last verified: 2015-09

Locations

AU (2); CA (2)