Trial Outcomes & Findings for TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure (NCT NCT03296813)

Last Updated: 2025-10-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2973 participants

Primary outcome timeframe

up to 30 months

Results posted on

2025-10-16

Participant Flow

2973 patients consented. 114 not randomized due to patient decision, PI decision, discharge before randomization occurred, died prior to randomization, or did not meet one or more eligibility criteria.

Participant milestones

Participant milestones
Measure	Torsemide Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: 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 Furosemide: Loop diuretic
Overall Study STARTED	1431	1428
Overall Study COMPLETED	1378	1368
Overall Study NOT COMPLETED	53	60

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Torsemide n=1431 Participants Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	Furosemide n=1428 Participants 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 Furosemide: Loop diuretic	Total n=2859 Participants Total of all reporting groups
Age, Continuous	64 years STANDARD_DEVIATION 14 • n=5 Participants	65 years STANDARD_DEVIATION 14 • n=7 Participants	64.5 years STANDARD_DEVIATION 14 • n=5 Participants
Sex: Female, Male Female	498 Participants n=5 Participants	557 Participants n=7 Participants	1055 Participants n=5 Participants
Sex: Female, Male Male	933 Participants n=5 Participants	871 Participants n=7 Participants	1804 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	75 Participants n=5 Participants	80 Participants n=7 Participants	155 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1355 Participants n=5 Participants	1345 Participants n=7 Participants	2700 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) Asian	37 Participants n=5 Participants	26 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) Black or African American	474 Participants n=5 Participants	494 Participants n=7 Participants	968 Participants n=5 Participants
Race (NIH/OMB) White	831 Participants n=5 Participants	837 Participants n=7 Participants	1668 Participants n=5 Participants
Race (NIH/OMB) More than one race	65 Participants n=5 Participants	58 Participants n=7 Participants	123 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	1431 Participants n=5 Participants	1428 Participants n=7 Participants	2859 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 30 months

Outcome measures

Outcome measures
Measure	Torsemide n=1431 Participants Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	Furosemide n=1428 Participants 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 Furosemide: Loop diuretic
All-cause Mortality, as Measured by Follow-up Phone Call or NDI	373 Participants	374 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Torsemide n=1431 Participants Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	Furosemide n=1428 Participants 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 Furosemide: Loop diuretic
All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)	677 Participants	704 Participants

SECONDARY outcome

Timeframe: up to 12 months

Population: Participants who had at least one re-hospitalization.

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 measures

Outcome measures
Measure	Torsemide n=536 Participants Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	Furosemide n=577 Participants 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 Furosemide: Loop diuretic
Total Re-hospitalizations, as Measured by Follow-up Phone Call	940 re-hospitalizations	987 re-hospitalizations

SECONDARY outcome

Timeframe: 30 days

All-cause mortality or all-cause hospitalization over 30 days

Outcome measures

Outcome measures
Measure	Torsemide n=1431 Participants Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	Furosemide n=1428 Participants 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 Furosemide: Loop diuretic
All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)	149 Participants	157 Participants

SECONDARY outcome

Timeframe: Baseline, 1 month, 6 months, 12 months

Population: Participants with both baseline and monthly KCCQ-CSS scores available (i.e., change from baseline at the month assessment could be analyzed).

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 measures

Outcome measures
Measure	Torsemide n=1431 Participants Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	Furosemide n=1428 Participants 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 Furosemide: Loop diuretic
Change in Health-related Quality of Life (QOL), as Measured by Follow-up Phone Call Baseline to Month 1	69.52 score on a scale Interval 67.53 to 71.51	68.22 score on a scale Interval 66.22 to 70.23
Change in Health-related Quality of Life (QOL), as Measured by Follow-up Phone Call Baseline to Month 6	70.61 score on a scale Interval 68.53 to 72.7	71.01 score on a scale Interval 68.91 to 73.1
Change in Health-related Quality of Life (QOL), as Measured by Follow-up Phone Call Baseline to Month 12	70.00 score on a scale Interval 67.85 to 72.15	69.98 score on a scale Interval 67.8 to 72.16

SECONDARY outcome

Timeframe: Month 1, month 6, month 12

Population: Participants with data available at each time point.

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 measures

Outcome measures
Measure	Torsemide n=1431 Participants Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	Furosemide n=1428 Participants 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 Furosemide: Loop diuretic
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2) Month 6 · PHQ-2 score < 3	658 Participants	672 Participants
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2) Month 6 · PHQ-2 score > = 3	113 Participants	119 Participants
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2) Month 12 · PHQ-2 score < 3	533 Participants	537 Participants
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2) Month 1 · PHQ-2 score > = 3	148 Participants	150 Participants
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2) Month 1 · PHQ-2 score < 3	790 Participants	813 Participants
Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2) Month 12 · PHQ-2 score > = 3	95 Participants	82 Participants

Adverse Events

Torsemide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 373 deaths

Furosemide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 374 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Robert Mentz, MD

Duke University

Phone: 919-668-7121

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place