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.
Brief Title
TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure
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.
* 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Heart Failure
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
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
Inclusion 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
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
Gender
All
Gender Based
false
Keywords
loop diuretic
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Estimated
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03296813
Org Class
Other
Org Full Name
Duke University
Org Study Id
Pro00080595
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure
Primary Outcomes
Outcome Description
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.
Outcome Measure
All-cause Mortality, as Measured by Follow-up Phone Call or NDI
Outcome Time Frame
up to 30 months
Secondary Ids
Secondary Id
U01HL125511-01A1
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
up to 12 months
Outcome Measure
All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)
Outcome Description
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).
Outcome Time Frame
up to 12 months
Outcome Measure
Total Re-hospitalizations, as Measured by Follow-up Phone Call
Outcome Description
All-cause mortality or all-cause hospitalization over 30 days
Outcome Time Frame
30 days
Outcome Measure
All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)
Outcome Description
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.
Outcome Time Frame
Baseline, 1 month, 6 months, 12 months
Outcome Measure
Change in Health-related Quality of Life (QOL), as Measured by Follow-up Phone Call
Outcome Description
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.
Outcome Time Frame
Month 1, month 6, month 12
Outcome Measure
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2)
See Also Links
Url
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sandhya Murthy
Investigator Email
smurthy@montefiore.org
Investigator Phone
718-904-3507
Categories Mesh Debug
Heart/Cardiovascular --- HEART FAILURE
Brain, Spinal Cord & Nervous System --- HEART DISEASES
Heart/Cardiovascular --- HEART DISEASES
Blood Disorders --- CARDIOVASCULAR DISEASES
Blood & Bone Marrow Cancers --- CARDIOVASCULAR DISEASES
Heart/Cardiovascular --- CARDIOVASCULAR DISEASES
MeSH Terms
HEART FAILURE
HEART DISEASES
CARDIOVASCULAR DISEASES
TORSEMIDE
FUROSEMIDE
SULFONAMIDES
AMIDES
ORGANIC CHEMICALS
SULFONES
SULFUR COMPOUNDS
PYRIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
SULFANILAMIDES
ANILINE COMPOUNDS
AMINES