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

September 29, 2025 updated by: Duke University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  • 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.

Study Type

Interventional

Enrollment (Actual)

2973

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Alexander City, Alabama, United States, 35010
        • Russel Medical Center
      • Huntsville, Alabama, United States, 35801
        • The Heart Center, PC
    • Arizona
      • Tucson, Arizona, United States, 85724
        • University of Arizona
    • California
      • Los Angeles, California, United States, 90073
        • V.A. Greater Los Angeles Healthcare System
      • San Francisco, California, United States, 94115
        • Kaiser Permanente Medical Center
    • Connecticut
      • Hartford, Connecticut, United States, 06105
        • Saint Francis Hospital and Medical Center
      • New Haven, Connecticut, United States, 06511
        • Yale
      • West Haven, Connecticut, United States, 06516
        • West Haven VA Medical Center
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Holy Cross Hospital
      • Gainesville, Florida, United States, 32610
        • University of Florida - Gainesville
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory Health Care
      • Augusta, Georgia, United States, 30912
        • Augusta University
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Queens Medical Center
    • Illinois
      • Aurora, Illinois, United States, 60506
        • Fox Valley Clinical Research Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago
      • Chicago, Illinois, United States, 60611
        • Northwestern Memorial Hospital
      • Maywood, Illinois, United States, 60153
        • Loyola University Medical Center
      • Peoria, Illinois, United States, 61606
        • Methodist Medical Center of Illinois
    • Indiana
      • Bloomington, Indiana, United States, 47402
        • Indiana University Health Bloomington Hospital
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Medical Center
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospitals and Clinics
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • University Medical Center
      • New Orleans, Louisiana, United States, 70121
        • Oschner Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • VA Medical Center/University of Maryland
      • Rockville, Maryland, United States, 20850
        • Shady Grove Medical Center
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Medical Center
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital
      • Ypsilanti, Michigan, United States, 48197
        • Saint Joseph Mercy Health System / Michigan Heart
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota
    • Mississippi
      • Jackson, Mississippi, United States, 29216
        • University of Mississippi Medical Center
    • Missouri
      • Springfield, Missouri, United States, 65807
        • Lester E. Cox Health Systems
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New Jersey
      • Pomona, New Jersey, United States, 08240
        • AtlantiCare Regional Medical Center
    • New York
      • Brooklyn, New York, United States, 11215
        • Presbyterian/Brooklyn Methodist Hospital
      • Manhasset, New York, United States, 11030
        • North Shore University Hospital
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10021
        • Weill Cornell Medical College
      • New York, New York, United States, 10029-6574
        • Mount Sinai
      • Stony Brook, New York, United States, 11794
        • Stony Brook University Hospital
      • The Bronx, New York, United States, 10461
        • Montefore Medical Center - Albert Einstein University Hospital
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina School of Medicine
      • Durham, North Carolina, United States, 27710
        • Duke (Duke Heart Center)
      • Matthews, North Carolina, United States, 28240
        • Novant Health Matthews Medical Center
      • Wilmington, North Carolina, United States, 28401
        • New Hanover Regional Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44106
        • University Hospitals Case Medical Center
    • Pennsylvania
      • Abington, Pennsylvania, United States, 19001
        • Abington Memorial Hospital
      • Ephrata, Pennsylvania, United States, 17522
        • Good Samaritan Hospital
      • Philadelphia, Pennsylvania, United States, 19102
        • Drexel University College of Medicine
      • Philadelphia, Pennsylvania, United States, 19107
        • Jefferson University Hospital
      • Wynnewood, Pennsylvania, United States, 19096
        • Main Line Health System
    • South Carolina
      • Greenville, South Carolina, United States, 29605
        • Greenville Hospital System University Medical Center
    • South Dakota
      • Rapid City, South Dakota, United States, 57701
        • Black Hills Cardiovascular Research
    • Texas
      • Dallas, Texas, United States, 75246
        • Baylor University Medical Center
    • Utah
      • Murray, Utah, United States, 84107
        • Intermountain Medical Center
      • Salt Lake City, Utah, United States, 84132
        • University of Utah Hospitals and Clinics
    • Virginia
      • Falls Church, Virginia, United States, 22042
        • Inova Health Care Services
      • Norfolk, Virginia, United States, 23507
        • Sentara Norfolk General Hospital
      • Richmond, Virginia, United States, 23298
        • Virginia Commonwealth University Health
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Torsemide
Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg.
Drug: Torsemide
Loop diuretic
Active Comparator: 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
Drug: Furosemide
Loop diuretic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause Mortality, as Measured by Follow-up Phone Call or NDI
Time Frame: up to 30 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)
Time Frame: up to 12 months
The time-to-event analysis of all-cause mortality or all-cause primary re-hospitalization was based on the time from randomization through death or the first primary re-hospitalization through 12 months. Patients who died or whose first all-cause re-hospitalization was after month 12 were censored at month 12. Patients who did not have a re-hospitalization and were alive were censored at the minimum of the time of the last re-hospitalization assessment or month 12.
up to 12 months
Total Re-hospitalizations, as Measured by Follow-up Phone Call
Time Frame: up to 12 months
Total all-cause primary re-hospitalization was defined as a hospitalization after the index hospitalization through month 12 that met one of the following criteria: 1.) at least a 24-hour stay (or a change in calendar date if the time of admission/discharge is not available) or 2.) reported as an in-patient admission by the patient/proxy with an admission date (complete or month and year) and no discharge date (i.e., length of stay could not be derived). Unit of measurement is the total number of re-hospitalizations for each subject (e.g., if a subject had 3 re-hospitalizations, then the outcome is 3 for the subject).
up to 12 months
All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)
Time Frame: 30 days
All-cause mortality or all-cause hospitalization over 30 days
30 days
Change in Health-related Quality of Life (QOL), as Measured by Follow-up Phone Call
Time Frame: Baseline, 1 month, 6 months, 12 months
QOL as assessed by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) (range, 0-100 with 100 indicating best health status). The KCCQ was administered prior to randomization (collected by the site) and at Months 1, 6 and 12 (ascertained at the Call Center visits). The outcome is the least square means in Torsemide and Furosemide groups where the difference = Torsemide mean minus Furosemide mean at the monthly assessment.
Baseline, 1 month, 6 months, 12 months
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2)
Time Frame: Month 1, month 6, month 12
Depression was assessed by the Patient Health Questionnaire-2 (PHQ-2) over 12 months. The PHQ-2 inquires about the frequency of depressed mood and anhedonia (inability to feel pleasure) over the past two weeks. The responses to the questions are scored 0 = Not at all, 1 = Several days, 2 = More than half the days, and 3 = Nearly every day. The PHQ-2 total score is obtained by adding the score for each question. The PHQ-2 total score ranges from 0-6. Reported as the number of patients with a total score <3 versus >=3.
Month 1, month 6, month 12

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)
Yale University

Investigators

  • Principal Investigator: Eric Velazquez, MD, Yale University
  • Principal Investigator: Robert Mentz, MD, Duke University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 11, 2018

Primary Completion (Actual)

July 29, 2022

Study Completion (Actual)

July 29, 2022

Study Registration Dates

First Submitted

September 26, 2017

First Submitted That Met QC Criteria

September 26, 2017

First Posted (Actual)

September 28, 2017

Study Record Updates

Last Update Posted (Estimated)

October 16, 2025

Last Update Submitted That Met QC Criteria

September 29, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00080595
  • U01HL125511-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Heart Failure

Clinical Trials on Torsemide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Kuwait

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe