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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a new extended-release version of torsemide, a medication that removes excess salt and water from the body, outperforms the regular version for individuals with stable heart failure. Researchers aim to determine if taking the extended-release version in the morning helps the body eliminate more sodium after meals compared to the immediate-release version. Individuals diagnosed with stable chronic heart failure and currently on a steady dose of certain diuretics (medications that help remove excess fluid) might be suitable candidates. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that torsemide, available in both immediate and extended-release forms, is generally well-tolerated by patients with heart failure. Studies comparing torsemide to furosemide, another common diuretic that helps remove excess fluid, suggest that torsemide may reduce hospital visits without increasing risk.

For immediate-release torsemide, research indicates it may lower the chance of hospital readmission for heart failure by 23% and could reduce the risk of death from any cause. These benefits suggest patients tolerate it well.

Extended-release torsemide has limited but encouraging data. Some studies suggest it might improve heart function over time without additional risks. Both forms of torsemide take longer to reach peak blood levels, which helps maintain steady effects with fewer side effects.

In summary, current research considers both versions of torsemide safe, with no major safety concerns reported. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart failure?

Researchers are excited about extended-release torsemide for heart failure because it offers a novel way to manage fluid retention with potentially improved outcomes. Unlike the standard of care diuretics, which often include medications like furosemide and immediate-release torsemide, the extended-release formulation is designed to provide a more consistent release of the medication over time. This could lead to better fluid balance and fewer hospital visits for heart failure patients. Additionally, by maintaining steady drug levels, it may reduce the risk of side effects commonly associated with fluctuating drug concentrations.

What evidence suggests that this trial's treatments could be effective for heart failure?

This trial will compare immediate-release torsemide with extended-release torsemide for heart failure. Research has shown that torsemide may improve heart failure symptoms and reduce hospital visits more effectively than furosemide. The immediate-release form has lowered heart failure-related hospitalizations. The extended-release form, which participants in this trial may receive, is designed to provide a steady effect over time, potentially leading to better removal of excess salt from the body. Although the extended-release version remains under study, early results are promising for better managing heart failure. ^{1 3 4 6 7}

Who Is on the Research Team?

Parta Hatamizadeh, MD, MPH

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8887994/

An evaluation of torsemide in patients with heart failure and ...

The limited current body of evidence indicates that torsemide may be superior to furosemide with respect to improving HF functional status and reducing HF ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT03214874

Within Subject Variability Study of ER Torsemide 20 mg ...

The study will evaluate the within-subject variability of 20mg ER torsemide as compared to 20mg IR torsemide (Demadex) in fully replicate double-crossover trial ...

3.

jamanetwork.com

jamanetwork.com/journals/jama/fullarticle/2800428

Effect of Torsemide vs Furosemide After Discharge on All ...

However, prior observational data demonstrated 1-year mortality rates following heart failure hospitalization of more than 30%. A meta-analysis ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12350330/

Comparative analysis of furosemide and torsemide efficacy ...

Both furosemide and torsemide demonstrated comparable efficacy in the initial treatment of AHF, as assessed by laboratory, ultrasound, and ...

5.

ahajournals.org

ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.064842

Effect of Torsemide Versus Furosemide on Symptoms and ...

Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 ...

6.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/nda/2022/213218Orig1s000ClinPharmR.pdf

213218Orig1s000 CLINICAL PHARMACOLOGY REVIEW(S)

Compared to DEMADEX, the median time to reach peaN torsemide plasma concentration is delayed by approximately 100 minutes following.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06708611

NCT06708611 | A Crossover Study of Patients with HF to ...

This is a randomized double-blind crossover study of the patients with stable heart failure, who are taking a loop diuretic. During the study period, the ...