TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure

NCT03296813 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: Pro00080595U01HL125511-01A1
• Study Type: interventional
• Target: 2,973
• Locations: 1 country
• Sites: 60

Brief Summary

TRANSFORM-HF is a large-scale, pragmatic, randomized, unblinded clinical effectiveness study comparing torsemide versus furosemide as treatment for heart failure. Approximately 6,000 patients with heart failure will be enrolled. The primary objective of the TRANSFORM-HF study is to compare the treatment strategy of torsemide versus furosemide on clinical outcomes over 12 months in patients with heart failure who are hospitalized.

Conditions

Heart Failure

Keywords

loop diuretic

Outcome Measures

Primary Outcomes (1)

• All-cause Mortality, as Measured by Follow-up Phone Call or NDI

  Death information was obtained from the Call Center through 30 months for patients 1-500, through 24 months for patients 501-1000, through 18 months for patients 1001-1500, and through 12 months for the remaining patients (except those who were randomized \< 12 months when the study was stopped by the DSMB). Also death information was obtained through searches of the 2018-2021 National Death Index (NDI) database.

  up to 30 months

Secondary Outcomes (5)

• All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)

  up to 12 months

• Total Re-hospitalizations, as Measured by Follow-up Phone Call

  up to 12 months

• All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)

  30 days

• Change in Health-related Quality of Life (QOL), as Measured by Follow-up Phone Call

  Baseline, 1 month, 6 months, 12 months

• Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2)

  Month 1, month 6, month 12

Study Arms (2)

Torsemide

ACTIVE COMPARATOR

Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg.

Drug: Torsemide

Furosemide

ACTIVE COMPARATOR

Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. For patients receiving loop diuretics other than furosemide, conversion to furosemide equivalents will be as follows: 1 mg oral torsemide = 2-4 mg oral furosemide 1 mg oral or intravenous bumetanide = 40 mg oral furosemide

Drug: Furosemide

Interventions

Torsemide DRUG

Loop diuretic

Torsemide

Furosemide DRUG

Loop diuretic

Furosemide

Eligibility Criteria

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

You may qualify if:

• Patient hospitalized (≥ 24 hours or over a change in calendar date) with worsening of chronic heart failure, or new diagnosis of heart failure AND meets one of the following criteria:
• Has a left ventricular ejection fraction (EF) ≤40% within 24 months prior to and including index hospitalization by any method (with most recent value used to determine eligibility)
• Has an elevated natriuretic peptide level (either NT-pro-B-type natriuretic peptide or B-type natriuretic peptide) during index hospitalization as measured by local laboratory (with most recent value used to determine eligibility)
• Plan for a daily outpatient oral loop diuretic regimen upon hospital discharge with anticipated need for long-term loop diuretic use
• ≥ 18 years of age
• Signed informed consent

You may not qualify if:

• End-stage renal disease requiring renal replacement therapy
• Inability or unwillingness to comply with the study requirements
• History of heart transplant or actively listed for heart transplant
• Implanted left ventricular assist device or implant anticipated \<3 months
• Pregnant or nursing women
• Malignancy or other non-cardiac condition limiting life expectancy to \<12 months
• Known hypersensitivity to furosemide, torsemide, or related agents

Sponsors & Collaborators

• Duke University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Yale University: collaborator

Study Sites (60)

Russel Medical Center

Alexander City, Alabama, 35010, United States

Location

The Heart Center, PC

Huntsville, Alabama, 35801, United States

Location

University of Arizona

Tucson, Arizona, 85724, United States

Location

V.A. Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

Kaiser Permanente Medical Center

San Francisco, California, 94115, United States

Location

Saint Francis Hospital and Medical Center

Hartford, Connecticut, 06105, United States

Location

Yale

New Haven, Connecticut, 06511, United States

Location

West Haven VA Medical Center

West Haven, Connecticut, 06516, United States

Location

Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

University of Florida - Gainesville

Gainesville, Florida, 32610, United States

Location

Emory Health Care

Atlanta, Georgia, 30322, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Queens Medical Center

Honolulu, Hawaii, 96813, United States

Location

Fox Valley Clinical Research Center

Aurora, Illinois, 60506, United States

Location

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Methodist Medical Center of Illinois

Peoria, Illinois, 61606, United States

Location

Indiana University Health Bloomington Hospital

Bloomington, Indiana, 47402, United States

Location

Indiana University Medical Center

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University Medical Center

New Orleans, Louisiana, 70112, United States

Location

Oschner Clinic

New Orleans, Louisiana, 70121, United States

Location

VA Medical Center/University of Maryland

Baltimore, Maryland, 21201, United States

Location

Shady Grove Medical Center

Rockville, Maryland, 20850, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Saint Joseph Mercy Health System / Michigan Heart

Ypsilanti, Michigan, 48197, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 29216, United States

Location

Lester E. Cox Health Systems

Springfield, Missouri, 65807, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

AtlantiCare Regional Medical Center

Pomona, New Jersey, 08240, United States

Location

Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York, 11215, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Mount Sinai

New York, New York, 10029-6574, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Montefore Medical Center - Albert Einstein University Hospital

The Bronx, New York, 10461, United States

Location

University of North Carolina School of Medicine

Chapel Hill, North Carolina, 27514, United States

Location

Duke (Duke Heart Center)

Durham, North Carolina, 27710, United States

Location

Novant Health Matthews Medical Center

Matthews, North Carolina, 28240, United States

Location

New Hanover Regional Medical Center

Wilmington, North Carolina, 28401, United States

Location

University Hospitals Case Medical Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Abington Memorial Hospital

Abington, Pennsylvania, 19001, United States

Location

Good Samaritan Hospital

Ephrata, Pennsylvania, 17522, United States

Location

Drexel University College of Medicine

Philadelphia, Pennsylvania, 19102, United States

Location

Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

Main Line Health System

Wynnewood, Pennsylvania, 19096, United States

Location

Greenville Hospital System University Medical Center

Greenville, South Carolina, 29605, United States

Location

Black Hills Cardiovascular Research

Rapid City, South Dakota, 57701, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

University of Utah Hospitals and Clinics

Salt Lake City, Utah, 84132, United States

Location

Inova Health Care Services

Falls Church, Virginia, 22042, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Virginia Commonwealth University Health

Richmond, Virginia, 23298, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (7)

• Rao VS, Cox ZL, Ivey-Miranda JB, Neville D, Balkcom N, Moreno-Villagomez J, Ramos-Mastache D, Maulion C, Bellumkonda L, Tang WHW, Collins SP, Velazquez EJ, Mentz RJ, Wilson FP, Turner JM, Wilcox CS, Ellison DH, Fang JC, Testani JM. Mechanistic Differences between Torsemide and Furosemide. J Am Soc Nephrol. 2025 Jan 1;36(1):99-107. doi: 10.1681/ASN.0000000000000481. Epub 2024 Aug 28.

  PMID: 39196651 DERIVED

• Kittipibul V, Mentz RJ, Clare RM, Wojdyla DM, Anstrom KJ, Eisenstein EL, Ambrosy AP, Goyal P, Skopicki HA, Ketema F, Kim DY, Desvigne-Nickens P, Pitt B, Velazquez EJ, Greene SJ. On-treatment analysis of torsemide versus furosemide for patients hospitalized for heart failure: A post-hoc analysis of TRANSFORM-HF. Eur J Heart Fail. 2024 Jul;26(7):1518-1523. doi: 10.1002/ejhf.3293. Epub 2024 May 15.

  PMID: 38745502 DERIVED

• Kapelios CJ, Greene SJ, Mentz RJ, Ikeaba U, Wojdyla D, Anstrom KJ, Eisenstein EL, Pitt B, Velazquez EJ, Fang JC; TRANSFORM-HF Investigators. Torsemide Versus Furosemide After Discharge in Patients Hospitalized With Heart Failure Across the Spectrum of Ejection Fraction: Findings From TRANSFORM-HF. Circ Heart Fail. 2024 Mar;17(3):e011246. doi: 10.1161/CIRCHEARTFAILURE.123.011246. Epub 2024 Mar 4.

  PMID: 38436075 DERIVED

• Greene SJ, Velazquez EJ, Anstrom KJ, Clare RM, DeWald TA, Psotka MA, Ambrosy AP, Stevens GR, Rommel JJ, Alexy T, Ketema F, Kim DY, Desvigne-Nickens P, Pitt B, Eisenstein EL, Mentz RJ; TRANSFORM-HF Investigators. Effect of Torsemide Versus Furosemide on Symptoms and Quality of Life Among Patients Hospitalized for Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. Circulation. 2023 Jul 11;148(2):124-134. doi: 10.1161/CIRCULATIONAHA.123.064842. Epub 2023 May 22.

  PMID: 37212600 DERIVED

• Mentz RJ, Anstrom KJ, Eisenstein EL, Sapp S, Greene SJ, Morgan S, Testani JM, Harrington AH, Sachdev V, Ketema F, Kim DY, Desvigne-Nickens P, Pitt B, Velazquez EJ; TRANSFORM-HF Investigators. Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. JAMA. 2023 Jan 17;329(3):214-223. doi: 10.1001/jama.2022.23924.

  PMID: 36648467 DERIVED

• Eisenstein EL, Sapp S, Harding T, Harrington A, Velazquez EJ, Mentz RJ, Greene SJ, Sachdev V, Kim DY, Anstrom KJ. Ascertaining Death Events in a Pragmatic Clinical Trial: Insights From the TRANSFORM-HF Trial. J Card Fail. 2022 Oct;28(10):1563-1567. doi: 10.1016/j.cardfail.2022.01.020. Epub 2022 Feb 16.

  PMID: 35181553 DERIVED

• Greene SJ, Velazquez EJ, Anstrom KJ, Eisenstein EL, Sapp S, Morgan S, Harding T, Sachdev V, Ketema F, Kim DY, Desvigne-Nickens P, Pitt B, Mentz RJ; TRANSFORM-HF Investigators. Pragmatic Design of Randomized Clinical Trials for Heart Failure: Rationale and Design of the TRANSFORM-HF Trial. JACC Heart Fail. 2021 May;9(5):325-335. doi: 10.1016/j.jchf.2021.01.013. Epub 2021 Mar 10.

  PMID: 33714745 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Heart Failure

Interventions

Torsemide; Furosemide

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfanilamides; Aniline Compounds; Amines

Results Point of Contact

• Title: Robert Mentz, MD
• Organization: Duke University

robert.mentz@duke.edu

919-668-7121

Study Officials

• Eric Velazquez, MD

  Yale University

  PRINCIPAL INVESTIGATOR

• Robert Mentz, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This study will be a randomized, unblinded, two-arm, multi-center clinical trial of patients with heart failure who are hospitalized. Patients will be randomized 1:1 to either oral torsemide OR oral furosemide prior to hospital discharge.

Study Record Dates

• First Submitted: September 26, 2017
• First Posted: September 28, 2017
• Study Start: July 11, 2018
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: October 16, 2025
• Results First Posted: October 16, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (60)