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

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: Heart Failure
• Intervention / Treatment: Drug: Torsemide; Drug: Furosemide

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): 2859
• Phase: Phase 3

Contacts and Locations

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
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Springfield, Missouri, United States, 65807
      • Lester E. Cox Health Systems
  • New Jersey
    • Pomona, New Jersey, United States, 08240
      • Atlanticare Regional Medical Center
  • New York
    • Bronx, New York, United States, 10461
      • Montefore Medical Center - Albert Einstein University Hospital
    • 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
  • 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

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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

How is the study designed?

Design Details

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

Number of Arms

2

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	All-cause mortality over a follow-up period of 12 months; subsets of patients to be evaluated at 6 month intervals to document vital status up to 30 months.	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	All-cause mortality or all-cause hospitalization over 12 months	12 months
Total hospitalizations, as measured by follow-up phone call	Total hospitalizations over 12 months	12 months
All-cause mortality or all-cause hospitalization, as measured by follow-up phone call	All-cause mortality or all-cause hospitalization over 30 days	30 days
Health-related quality of life, as measured by follow-up phone call	Health-related quality of life over 12 months	12 months
Symptoms of depression, as measured by follow-up phone call	Symptoms of depression over 12 months	12 months

Collaborators and Investigators

• 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

General Publications

• 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.
• 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.

Helpful Links

• Related Info
• TRANSFORM-HF study website

Study record dates

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 (Actual): August 19, 2022
• Last Update Submitted That Met QC Criteria: August 17, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: loop diuretic
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Furosemide; Torsemide
• 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