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

NCT ID: NCT03296813

Last Updated: 2025-10-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

2973 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-11

Study Completion Date

2022-07-29

Brief Summary

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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.

Detailed Description

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* This study will be a randomized, unblinded, two-arm, multi-center clinical trial of patients with heart failure who are hospitalized. Heart failure need not be the reason for hospitalization. Patients will be randomized 1:1 to either oral torsemide OR oral furosemide prior to hospital discharge. Oral dosing of torsemide compared to furosemide will be 1mg:2mg. The specific loop diuretic dose will be at the discretion of the treating physician with the above noted conversion.
* Trial enrollment occurs before hospital discharge, at the discretion of the healthcare provider.
* As appropriate, adherence to the randomized medication will be encouraged during the remainder of hospitalization and will continue post-discharge. Patients will receive follow-up per standard care without any additional study-specific visits.
* Patients will have 30-day, 6-month and 12-month follow-up phone contacts for assessments of vital status, interval hospitalizations, adherence, and quality of life. "Central follow-up" and collection of hospital discharge summaries via IRB-approved mechanisms. Subsets of patients enrolled early in the study have additional phone contacts beyond 12 months, up to 30 months, at six month intervals, to document vital status.

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Torsemide

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

Group Type ACTIVE_COMPARATOR

Torsemide

Intervention Type DRUG

Loop diuretic

Furosemide

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

Group Type ACTIVE_COMPARATOR

Furosemide

Intervention Type DRUG

Loop diuretic

Interventions

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Torsemide

Loop diuretic

Intervention Type DRUG

Furosemide

Loop diuretic

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. 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:

1. 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)
2. 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)
2. Plan for a daily outpatient oral loop diuretic regimen upon hospital discharge with anticipated need for long-term loop diuretic use
3. ≥ 18 years of age
4. Signed informed consent

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Yale University

OTHER

Sponsor Role collaborator

Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eric Velazquez, MD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Robert Mentz, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

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Russel Medical Center

Alexander City, Alabama, United States

Site Status

The Heart Center, PC

Huntsville, Alabama, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

V.A. Greater Los Angeles Healthcare System

Los Angeles, California, United States

Site Status

Kaiser Permanente Medical Center

San Francisco, California, United States

Site Status

Saint Francis Hospital and Medical Center

Hartford, Connecticut, United States

Site Status

Yale

New Haven, Connecticut, United States

Site Status

West Haven VA Medical Center

West Haven, Connecticut, United States

Site Status

Holy Cross Hospital

Fort Lauderdale, Florida, United States

Site Status

University of Florida - Gainesville

Gainesville, Florida, United States

Site Status

Emory Health Care

Atlanta, Georgia, United States

Site Status

Augusta University

Augusta, Georgia, United States

Site Status

Queens Medical Center

Honolulu, Hawaii, United States

Site Status

Fox Valley Clinical Research Center

Aurora, Illinois, United States

Site Status

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Loyola University Medical Center

Maywood, Illinois, United States

Site Status

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Site Status

Indiana University Health Bloomington Hospital

Bloomington, Indiana, United States

Site Status

Indiana University Medical Center

Indianapolis, Indiana, United States

Site Status

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status

University Medical Center

New Orleans, Louisiana, United States

Site Status

Oschner Clinic

New Orleans, Louisiana, United States

Site Status

VA Medical Center/University of Maryland

Baltimore, Maryland, United States

Site Status

Shady Grove Medical Center

Rockville, Maryland, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Henry Ford Hospital

Detroit, Michigan, United States

Site Status

Saint Joseph Mercy Health System / Michigan Heart

Ypsilanti, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

Lester E. Cox Health Systems

Springfield, Missouri, United States

Site Status

Washington University School of Medicine

St Louis, Missouri, United States

Site Status

AtlantiCare Regional Medical Center

Pomona, New Jersey, United States

Site Status

Presbyterian/Brooklyn Methodist Hospital

Brooklyn, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Stony Brook University Hospital

Stony Brook, New York, United States

Site Status

Montefore Medical Center - Albert Einstein University Hospital

The Bronx, New York, United States

Site Status

University of North Carolina School of Medicine

Chapel Hill, North Carolina, United States

Site Status

Duke (Duke Heart Center)

Durham, North Carolina, United States

Site Status

Novant Health Matthews Medical Center

Matthews, North Carolina, United States

Site Status

New Hanover Regional Medical Center

Wilmington, North Carolina, United States

Site Status

University Hospitals Case Medical Center

Cleveland, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Abington Memorial Hospital

Abington, Pennsylvania, United States

Site Status

Good Samaritan Hospital

Ephrata, Pennsylvania, United States

Site Status

Drexel University College of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

Main Line Health System

Wynnewood, Pennsylvania, United States

Site Status

Greenville Hospital System University Medical Center

Greenville, South Carolina, United States

Site Status

Black Hills Cardiovascular Research

Rapid City, South Dakota, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

University of Utah Hospitals and Clinics

Salt Lake City, Utah, United States

Site Status

Inova Health Care Services

Falls Church, Virginia, United States

Site Status

Sentara Norfolk General Hospital

Norfolk, Virginia, United States

Site Status

Virginia Commonwealth University Health

Richmond, Virginia, United States

Site Status

Froedtert Hospital

Milwaukee, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 39196651 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38745502 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38436075 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37212600 (View on PubMed)

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.

Reference Type DERIVED
PMID: 36648467 (View on PubMed)

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.

Reference Type DERIVED
PMID: 35181553 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33714745 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

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http://dcri.org

Related Info

Other Identifiers

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U01HL125511-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

Pro00080595

Identifier Type: -

Identifier Source: org_study_id

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