TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORMan... | NCT03296813

ID	Type	Description	Link
U01HL125511-01A1	U.S. NIH Grant/Contract		View source

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
Yale University	OTHER

TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORMan... | NCT03296813 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Torsemide	Active Comparator	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg.	Drug: Torsemide
Furosemide	Active Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
Torsemide	Drug	Loop diuretic	Torsemide
Furosemide

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
All-cause Mortality, as Measured by Follow-up Phone Call or NDI	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 Outcomes

Measure	Description	Time Frame
All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)	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.

Contacts/Locations Module

Name	Affiliation	Role
Eric Velazquez, MD	Yale University	Principal Investigator
Robert Mentz, MD	Duke University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Russel Medical Center		Alexander City	Alabama	35010	United States
The Heart Center, PC

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
42419438	Derived	Tong G, Zeng Y, Greene SJ, Anstrom KJ, Testani J, Mentz RJ, Li F, Velazquez EJ. Comparative effectiveness of torsemide vs furosemide in the management of heart failure patients: win-ratio reanalysis of the TRANSFORM-HF trial. Am Heart J. 2026 Jul 8:107525. doi: 10.1016/j.ahj.2026.107525. Online ahead of print.
39196651	Derived	Rao VS, Cox ZL, Ivey-Miranda JB, Neville D, Balkcom N, Moreno-Villagomez J, Ramos-Mastache D, Maulion C, Bellumkonda L, Tang WHW, Collins SP, Velazquez EJ, Mentz RJ, Wilson FP, Turner JM, Wilcox CS, Ellison DH, Fang JC, Testani JM. Mechanistic Differences between Torsemide and Furosemide. J Am Soc Nephrol. 2025 Jan 1;36(1):99-107. doi: 10.1681/ASN.0000000000000481. Epub 2024 Aug 28.

Label	URL
Related Info	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
FG001	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 23, 2018

Arm/Group Information

ID	Title	Description
BG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
BG001	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
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00064± 14 BG00165± 14 BG00264.5± 14

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000498 BG001557 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00075 BG00180 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0009 BG0013 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0001431 BG0011428 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

All-cause Mortality, as Measured by Follow-up Phone Call or NDI

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.

Posted

Count of Participants

Participants

up to 30 months

ID	Title	Description
OG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
OG001	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

Units	Counts
Participants	OG0001431 OG0011428

Title

Denominators

Categories

Title	Measurements
	OG000373 OG001374

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	To determine whether torsemide is superior to furosemide with respect to all-cause mortality among patients hospitalized for heart failure.	Regression, Cox		0.765	P-value not adjusted for multiple comparisons.	Hazard Ratio (HR)	1.022			2-Sided	95	0.885	1.180					Superiority		P-value from a Cox proportional hazards regression model including the assigned treatment (torsemide vs. furosemide as the reference group) as well as age, sex, baseline ejection fraction (<40%, 41-49%, >50%, unknown), and loop diuretic treatment prior to index hospital admission as covariates.

Secondary

All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)

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.

Posted

Count of Participants

Participants

up to 12 months

ID	Title	Description
OG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
OG001	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

Units	Counts
Participants

Secondary

Total Re-hospitalizations, as Measured by Follow-up Phone Call

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).

Participants who had at least one re-hospitalization.

Posted

Number

re-hospitalizations

up to 12 months

ID	Title	Description
OG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
OG001	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

Secondary

All-cause Mortality or All-cause Hospitalization, as Measured by Follow-up Phone Call or NDI (for Death)

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

Posted

Count of Participants

Participants

30 days

ID	Title	Description
OG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
OG001	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

Units	Counts
Participants	OG000

Secondary

Change in Health-related Quality of Life (QOL), as Measured by Follow-up Phone Call

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.

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

Posted

Least Squares Mean

95% Confidence Interval

score on a scale

Baseline, 1 month, 6 months, 12 months

ID	Title	Description
OG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
OG001	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

Secondary

Symptoms of Depression as Measured by the Patient Health Questionnaire-2 (PHQ-2)

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.

Participants with data available at each time point.

Posted

Count of Participants

Participants

Month 1, month 6, month 12

ID	Title	Description
OG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic
OG001	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

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Torsemide	Oral dosing of torsemide compared to furosemide will be 1mg:2-4mg. Torsemide: Loop diuretic	373	1,431	0	0	0	0
EG001	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	374	1,428	0	0	0	0

Ancestor Terms

ID	Term
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457	Sulfur Compounds
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D013424	Sulfanilamides
D000814	Aniline Compounds
D000588	Amines

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	To determine whether torsemide is superior to furosemide with respect to all-cause mortality or first all-cause hospitalization through month 12 among patients hospitalized for heart failure.	Regression, Cox		0.113	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Hazard Ratio (HR)	0.918			2-Sided	95	0.826	1.020					Superiority		P-value from a Cox proportional hazards regression model including the assigned treatment (torsemide vs. furosemide as the reference group) as well as age, sex, baseline ejection fraction (<40%, 41-49%, >50%, unknown), and loop diuretic treatment prior to index hospital admission as covariates.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	To determine whether torsemide is superior to furosemide with respect to total all-cause hospitalizations through month 12 among patients hospitalized for heart failure.	Regression, Linear		0.366	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Risk Ratio (RR)	0.945			2-Sided	95	0.836	1.068					Superiority		P-value from a negative binomial regression of the frequency of re-hospitalizations with an offset term of the log of each subject's months to last re-hospitalization assessment through month 12. Re-hospitalizations greater than or equal to 5 were combined and analyzed with re-hospitalizations = 5 (i.e., one category >=5) and for the subjects with >=5 re-hospitalizations, the offset term was the log of the months to the 5th re-hospitalization.

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	To determine whether torsemide is superior to furosemide with respect to all-cause mortality or first all-cause hospitalization through day 30 among patients hospitalized for heart failure.	Regression, Cox		0.610	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Hazard Ratio (HR)	0.943			2-Sided	95	0.753	1.181					Superiority		P-value from a Cox proportional hazards regression model including the assigned treatment (torsemide vs. furosemide as the reference group) as well as age, sex, baseline ejection fraction (<40%, 41-49%, >50%, unknown), and loop diuretic treatment prior to index hospital admission as covariates.

Title

Denominators

Categories

Baseline to Month 1

- ParticipantsOG000981
- ParticipantsOG001996

Title	Measurements
	OG00069.52(67.53 to 71.51) OG00168.22(66.22 to 70.23)

Baseline to Month 6

- ParticipantsOG000800
- ParticipantsOG001826

Title	Measurements
	OG00070.61(68.53 to 72.70) OG001

Baseline to Month 12

- ParticipantsOG000665
- ParticipantsOG001656

Title	Measurements
	OG00070.00(67.85 to 72.15) OG001

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Non-Inferiority Type	Other Analysis Description
OG000 OG001	To determine whether torsemide improves the QOL at 1 month compared to Furosemide as assessed by the KCCQ among patients hospitalized for heart failure.	Mixed Models Analysis	0.194	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Mean Difference (Final Values)	1.30	2-Sided	95	-0.66	3.26	Superiority	Least squares means results from mixed-model repeated measures analysis of the KCCQ score change from baseline with terms for treatment, time (visit) from randomization, treatment x time (visit) interaction as well as the baseline KCCQ score, age, sex, baseline ejection fraction (<40%, 41-49%, >50%, unknown), and loop diuretic treatment prior to index hospital admission as covariates.
OG000 OG001	To determine whether torsemide improves the QOL at 6 months compared to Furosemide as assessed by the KCCQ among patients hospitalized for heart failure.	Mixed Models Analysis	0.718	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Mean Difference (Final Values)	-0.39	2-Sided	95	-2.53	1.74	Superiority	Least squares means results from mixed-model repeated measures analysis of the KCCQ score change from baseline with terms for treatment, time (visit) from randomization, treatment x time (visit) interaction as well as the baseline KCCQ score, age, sex, baseline ejection fraction (<40%, 41-49%, >50%, unknown), and loop diuretic treatment prior to index hospital admission as covariates.
OG000 OG001	To determine whether torsemide improves the QOL at 12 months compared to Furosemide as assessed by the KCCQ among patients hospitalized for heart failure.	Mixed Models Analysis	0.987	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Mean Difference (Final Values)	0.02	2-Sided	95	-2.26	2.30	Superiority	Least squares means results from mixed-model repeated measures analysis of the KCCQ score change from baseline with terms for treatment, time (visit) from randomization, treatment x time (visit) interaction as well as the baseline KCCQ score, age, sex, baseline ejection fraction (<40%, 41-49%, >50%, unknown), and loop diuretic treatment prior to index hospital admission as covariates.

Title

Denominators

Categories

Month 1

- ParticipantsOG000938
- ParticipantsOG001963

Title	Measurements
PHQ-2 score < 3	OG000790 OG001813
PHQ-2 score > = 3	OG000148 OG001150

Month 6

- ParticipantsOG000771
- ParticipantsOG001791

Title	Measurements
PHQ-2 score < 3	OG000658 OG001

Month 12

- ParticipantsOG000628
- ParticipantsOG001619

Title	Measurements
PHQ-2 score < 3	OG000533 OG001

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Non-Inferiority Type
OG000 OG001	To determine whether torsemide reduces symptoms of depression at 1 month compared to Furosemide as assessed by the PHQ-2 among patients hospitalized for heart failure.	Wilcoxon (Mann-Whitney)	0.904	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Superiority
OG000 OG001	To determine whether torsemide reduces symptoms of depression at 6 months compared to Furosemide as assessed by the PHQ-2 among patients hospitalized for heart failure.	Wilcoxon (Mann-Whitney)	0.829	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Superiority
OG000 OG001	To determine whether torsemide reduces symptoms of depression at 12 months compared to Furosemide as assessed by the PHQ-2 among patients hospitalized for heart failure.	Wilcoxon (Mann-Whitney)	0.342	For secondary analyses, a statistically significant p-value < 0.005 was pre-specified to address the multiple planned analyses and help control the overall type I error rate.	Superiority

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases