Immediate vs Extended Release Torsemide for Heart Failure

Overseen By Sophia Shah, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Florida

Must be taking: Loop diuretics

Must not be taking: Non-loop diuretics

Disqualifiers: Recent MI, Stroke, AKI, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Trial Summary

What is the purpose of this trial?

The goal of this randomized double-blind crossover study is to assess whether a morning dose of the extended release torsemide has a better efficacy than the ordinary immediate release torsemide to induce renal sodium excretion after a salty lunch in patients with stable heart failure. The main questions it aims to answer are: * Are the amounts of excreted sodium in the urine during the 2- and 6-hours' time period after a morning dose of extended release torsemide different from the amounts after the immediate release torsemide. * Are the amounts of excreted sodium in the urine during the 2- and 6-hours' time period after a salty lunch, which will be consumed approximately 6 hours following a morning dose of extended release torsemide, different from the amounts after the immediate release torsemide. * Is the amount of excreted sodium in the urine during the 24 hours' time period after a salty lunch, which will be consumed approximately 6 hours following a morning dose of extended release torsemide, different from the amount after the immediate release torsemide. Participants will be asked to: * Start taking daily immediate release or extended release torsemide tablets that is provided to them. * Eat the meals with standard contents of sodium that is provided to them and avoid other meals, drinks (except for water) and snacks for the duration of the study. * Collect urine for 24 hours, after approximately one week of the initiation of the study medication. * Go to the clinical research center the day that the 24-hour urine collection is finished and stay there throughout the day to receive standard meals and to have blood and urine samples collected. * Switch torsemide pills to the new one that will be dispensed to them at the clinical research center. If they were taking the immediate release torsemide during the first part, then they will be given the sustained release torsemide and vice versa. The study is double blind; therefore, the subjects, study coordinators, and investigators are unaware of whether each subject is on immediate release torsemide first or on extended release torsemide first. * Collect urine for an additional 12 hours after leaving the clinical research center to be sent to the clinical research center the next morning. * Continue to take the provided meals and to avoid other meals, drinks (except for water) and snacks. * Again, collect urine for 24 hours, after approximately one week, take that to the clinical research center when the 24-hour collection is completed and stay there throughout the day to receive standard meals and to have blood and urine samples collected. * Collect urine for an additional 12 hours to be sent to the clinical research center the next morning. Researchers will compare the amount of sodium excretion when each subject is taking immediate release torsemide versus the time that the same subject is taking extended release torsemide.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires that you continue taking a stable dose of certain heart failure medications like furosemide, torsemide, or bumetanide. You should not have any changes in your heart failure medications during the study.

What data supports the effectiveness of the drug Torsemide for heart failure?

Research shows that Torsemide, compared to Furosemide, significantly reduces hospital readmissions for heart failure and has a more predictable absorption, which may lead to better clinical outcomes. ^{1 2 3 4 5}

How does the drug torsemide differ from other treatments for heart failure?

Torsemide is a loop diuretic with a longer duration of action and higher bioavailability than furosemide, the most commonly used diuretic for heart failure. It also has additional benefits like improving heart function and reducing hospitalizations and mortality, making it a promising option for better managing heart failure. ^{1 2 3 6 7}

Research Team

Parta Hatamizadeh, MD, MPH

Principal Investigator

University of Florida

Eligibility Criteria

This trial is for adults over 18 with stable chronic heart failure, who've been on a steady dose of certain diuretics. They must be able to eat a high-sodium diet and not change their heart failure meds during the study.

Inclusion Criteria

Optimum volume status determined by experienced physician

My heart failure condition has been stable for the last month.

Willing and able to sign the informed consent

Exclusion Criteria

Refusal or inability to sign the informed consent

I need to take a pain reliever other than low dose aspirin.

I have had sudden lung swelling or heart issues due to amyloid.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment Phase 1

Participants receive either immediate release or extended release torsemide for approximately one week, followed by urine collection and clinical assessments.

1 week

1 visit (in-person) for urine collection and assessments

Crossover and Treatment Phase 2

Participants switch to the alternate torsemide formulation and continue treatment for another week, followed by urine collection and clinical assessments.

1 week

1 visit (in-person) for urine collection and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Torsemide

Trial Overview The study compares two forms of torsemide: immediate release versus extended release, after eating a salty meal. It's double-blind and crossover, meaning patients switch between treatments without knowing which they're taking.

Participant Groups

Group I: Extended release torsemide Experimental Treatment 2 Interventions

Group II: Immediate release torsemide Active Control 2 Interventions

Torsemide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Torsemide for:

• Edema
• Heart Failure
• Renal Failure
• High Blood Pressure
• Ascites
• Nonobstructive Oliguria

Approved in European Union as Torasemide for:

• Edema
• Heart Failure
• Liver Disease
• Kidney Disease

Approved in Canada as Torsemide for:

• Edema
• Heart Failure
• Renal Failure
• High Blood Pressure

Approved in Japan as Torasemide for:

• Edema
• Heart Failure
• Liver Disease
• Kidney Disease

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Sarfez Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Recruited

100+

Findings from Research

In a systematic review of two randomized trials involving 471 patients with systolic heart failure, torsemide was found to significantly reduce total heart failure readmissions by 59% compared to furosemide.

Torsemide also decreased cardiovascular readmissions by 23% and showed a trend towards reducing all-cause mortality, suggesting it may be a more effective option for managing heart failure than furosemide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should torsemide be the loop diuretic of choice in systolic heart failure? DiNicolantonio, JJ.[2018]

Torasemide shows significant advantages over furosemide in treating heart failure, including reduced hospitalizations, improved functional status, and enhanced quality of life for patients.

Torasemide has a more favorable safety profile, with a lower risk of hypokalemia compared to furosemide, making it a better option for patients with symptomatic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LOOP DIURETICS IN HEART FAILURE: EVIDENCE-BASED CHOICE. Rоsul, ММ., Bletskan, ММ., Ivano, NV., et al.[2021]

In a study of 234 patients with chronic heart failure, those treated with torsemide had significantly lower rates of hospital readmission for heart failure (17% vs. 32% for furosemide) and for all cardiovascular causes (44% vs. 59%).

Patients on torsemide also experienced fewer hospital days for heart failure (106 days vs. 296 days for furosemide) and reported greater improvements in fatigue, suggesting that torsemide may be a more effective diuretic for managing chronic heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. Murray, MD., Deer, MM., Ferguson, JA., et al.[2019]

In a study involving 2859 hospitalized heart failure patients, torsemide did not significantly reduce all-cause mortality compared to furosemide, with similar death rates in both groups (26.1% for torsemide vs. 26.2% for furosemide).

Both diuretics showed comparable rates of all-cause hospitalization, indicating that torsemide may not offer a clear advantage over furosemide in managing heart failure outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. Mentz, RJ., Anstrom, KJ., Eisenstein, EL., et al.[2023]

In a study involving 7 dogs with stable congestive heart failure (CHF), torsemide was found to be as effective as furosemide in controlling clinical signs of CHF, with indications of greater diuresis.

Torsemide treatment led to significant changes in several laboratory parameters, suggesting it may have a different impact on kidney function and electrolyte balance compared to furosemide, but did not affect the quality of life of the dogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. Peddle, GD., Singletary, GE., Reynolds, CA., et al.[2018]

Torasemide, a newer loop diuretic, has a longer half-life and higher bioavailability than furosemide, and it also offers additional benefits like anti-aldosterone effects and vasorelaxation.

Clinical studies suggest that torasemide not only improves left ventricular function but also reduces mortality and hospitalizations related to heart failure, enhancing patients' quality of life and exercise tolerance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Torasemide for the treatment of heart failure. Ishido, H., Senzaki, H.[2019]

In a systematic review of 19 studies involving 19,280 heart failure patients, torsemide was associated with a significant improvement in functional status and a lower risk of cardiac mortality compared to furosemide.

Torsemide also showed a trend towards fewer hospitalizations due to heart failure, although this result was not statistically significant, indicating it may be a more effective diuretic option for heart failure management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure. Abraham, B., Megaly, M., Sous, M., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Should torsemide be the loop diuretic of choice in systolic heart failure? [2018]

2. Poland pubmed.ncbi.nlm.nih.gov

LOOP DIURETICS IN HEART FAILURE: EVIDENCE-BASED CHOICE. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Effect of torsemide and furosemide on clinical, laboratory, radiographic and quality of life variables in dogs with heart failure secondary to mitral valve disease. [2018]

6. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Torasemide for the treatment of heart failure. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure. [2020]