Clinical trial NCT03296813: TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure
Official title: TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Heart Failure
Keywords: loop diuretic
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Yale University
First posted: 2017-09-28
Enrollment: 2859
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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 purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: All-cause mortality, as measured by follow-up phone call
timeFrame: 30 months
Secondary outcomes:
measure: All-cause mortality or all-cause hospitalization, as measured by follow-up phone call
timeFrame: 12 months
measure: Total hospitalizations, as measured by follow-up phone call
timeFrame: 12 months
measure: All-cause mortality or all-cause hospitalization, as measured by follow-up phone call
timeFrame: 30 days
measure: Health-related quality of life, as measured by follow-up phone call
timeFrame: 12 months
measure: Symptoms of depression, as measured by follow-up phone call
timeFrame: 12 months
Other outcomes:
Locations:
city: Alexander City
country: United States
facility: Russel Medical Center
state: Alabama
city: Huntsville
country: United States
facility: The Heart Center, PC
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Los Angeles
country: United States
facility: V.A. Greater Los Angeles Healthcare System
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Hartford
country: United States
facility: Saint Francis Hospital and Medical Center
state: Connecticut
city: New Haven
country: United States
facility: Yale
state: Connecticut
city: West Haven
country: United States
facility: West Haven VA Medical Center
state: Connecticut
city: Fort Lauderdale
country: United States
facility: Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Atlanta
country: United States
facility: Emory Health Care
state: Georgia
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Honolulu
country: United States
facility: Queens Medical Center
state: Hawaii
city: Aurora
country: United States
facility: Fox Valley Clinical Research Center
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Bloomington
country: United States
facility: Indiana University Health Bloomington Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Medical Center
state: Indiana
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: New Orleans
country: United States
facility: University Medical Center
state: Louisiana
city: New Orleans
country: United States
facility: Oschner Clinic
state: Louisiana
city: Baltimore
country: United States
facility: VA Medical Center/University of Maryland
state: Maryland
city: Rockville
country: United States
facility: Shady Grove Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Ypsilanti
country: United States
facility: Saint Joseph Mercy Health System / Michigan Heart
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Springfield
country: United States
facility: Lester E. Cox Health Systems
state: Missouri
city: Pomona
country: United States
facility: AtlantiCare Regional Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefore Medical Center - Albert Einstein University Hospital
state: New York
city: Brooklyn
country: United States
facility: Presbyterian/Brooklyn Methodist Hospital
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University Hospital
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina School of Medicine
state: North Carolina
city: Durham
country: United States
facility: Duke (Duke Heart Center)
state: North Carolina
city: Matthews
country: United States
facility: Novant Health Matthews Medical Center
state: North Carolina
city: Wilmington
country: United States
facility: New Hanover Regional Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Abington
country: United States
facility: Abington Memorial Hospital
state: Pennsylvania
city: Ephrata
country: United States
facility: Good Samaritan Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Drexel University College of Medicine
state: Pennsylvania
city: Philadelphia
country: United States
facility: Jefferson University Hospital
state: Pennsylvania
city: Wynnewood
country: United States
facility: Main Line Health System
state: Pennsylvania
city: Greenville
country: United States
facility: Greenville Hospital System University Medical Center
state: South Carolina
city: Rapid City
country: United States
facility: Black Hills Cardiovascular Research
state: South Dakota
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Hospitals and Clinics
state: Utah
city: Falls Church
country: United States
facility: Inova Health Care Services
state: Virginia
city: Norfolk
country: United States
facility: Sentara Norfolk General Hospital
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Health
state: Virginia
city: Milwaukee
country: United States
facility: Froedtert Hospital
state: Wisconsin
Study officials:
affiliation: Yale University
name: Eric Velazquez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Robert Mentz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.