Torsemide for Heart Failure

(EXTOR-HF Trial)

Overseen By Chris Wilcox, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Sarfez Pharmaceuticals, Inc.

Must be taking: 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

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines torsemide, a medicine for heart failure, to determine how different forms affect the body's ability to eliminate salt after a salty meal. Participants will use both the immediate-release and extended-release versions to compare effects. This trial suits individuals with stable heart failure who have taken a loop diuretic (a type of water pill) for at least a month. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

You will need to stop your current loop diuretic and switch to torsemide for the study. Other heart failure medications should not change during the study.

What is the safety track record for torsemide?

Research has shown that torsemide, in both long-acting and quick-acting forms, is generally well-tolerated. Studies comparing torsemide to furosemide, a common diuretic, found that torsemide users experienced fewer hospital visits for heart issues and fewer medication side effects. This suggests torsemide might be a safer option for those with heart failure.

While information on long-acting torsemide remains limited, it may improve heart function and lower the risk of heart problems. Quick-acting torsemide has reduced hospital stays for heart issues and overall compared to furosemide. Importantly, there was no increase in the risk of death, providing reassurance for those considering trial participation. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about torsemide for heart failure because it offers a new extended-release formula that may enhance patient convenience and medication adherence. Unlike the standard immediate-release versions, which require more frequent dosing, the extended-release torsemide allows for once-daily dosing, potentially improving quality of life for patients. This new delivery method could help maintain more consistent drug levels in the body, potentially improving heart failure management.

What is the effectiveness track record for torsemide in treating heart failure?

Research has shown that torsemide might work better than furosemide, another common water pill, for people with heart failure. Studies have found that torsemide can reduce the risk of returning to the hospital for heart problems by 23%. It also appears to lower the chance of dying from any cause. This trial tests both the immediate release and extended release versions of torsemide in separate treatment arms, and both show promise for improving heart health. Evidence suggests that torsemide could be a better option for managing heart failure symptoms and outcomes. ^{1 2 3 6 7}

Who Is on the Research Team?

Sophia Shah, MD

Principal Investigator

Safez Pharmaceuticals

Nayle A Ancares, MD

Principal Investigator

Future Life Clinical Trials

Are You a Good Fit for This Trial?

This trial is for men and women over 18 with stable heart failure, who have been on loop diuretics like furosemide. They must not expect to change their heart failure meds during the study and agree to use birth control if applicable. It's not for those with recent severe cardiac or kidney events, uncontrolled diabetes or hypertension, certain lung diseases, urinary issues, very low kidney function, a history of specific heart conditions, or breastfeeding women.

Inclusion Criteria

I am over 18 years old.

I am a woman who can have children, not pregnant, and will use birth control during the study.

I have been taking water pills for the last 30 days.

Exclusion Criteria

I am not taking diuretics other than spironolactone, eplerenone, finerenone, or SGLT2 inhibitors.

I haven't had a heart attack, stroke, mini-stroke, severe kidney injury, or heart failure that required hospitalization in the last 30 days.

I have severe lung problems not related to heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either immediate release or extended release torsemide for one week, followed by a single dose administration and sodium excretion measurement

1 week

1 visit (in-person) for dosing and measurement

Crossover

Participants switch to the alternate form of torsemide and repeat the dosing and measurement process

1 week

1 visit (in-person) for dosing and measurement

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 tests immediate release (IR) versus extended release (ER) Torsemide in patients with stable heart failure already taking loop diuretics. Participants will switch from their current medication to IR/ER Torsemide for one week and then receive a single dose at the site where sodium excretion post-dosing and after a high salt meal will be measured.

How Is the Trial Designed?

Group I: Extended release torsemide Experimental Treatment 1 Intervention

Drug: Extended release torsemide 24 mg tablet. Subjects will receive oral dose of 24 mg extended release torsemide tablet and a placebo of 20 mg immediate release torsemide.

Group II: Immediate release torsemide Active Control 1 Intervention

Drug: Immediate release torsemide 20 mg tablet. Subjects will receive oral dose of 20 mg of immediate release torsemide and a placebo of 24 mg extended release torsemide.

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?

Sarfez Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Recruited

100+

Published Research Related to This Trial

Disopyramide phosphate can be effective in treating ventricular arrhythmias in patients with ischemic cardiomyopathy and congestive heart failure, but it may lead to elevated plasma levels that cause serious side effects.

In this case, the patient experienced ventricular tachycardia and prolonged QRS and QT intervals, indicating that disopyramide can negatively affect heart conduction, especially in patients with heart failure or kidney/liver issues, necessitating careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Disopyramide-induced ventricular tachycardia. Lo, KS., Gantz, KB., Stetson, PL., et al.[2013]

In the EMPEROR-Reduced study involving over 3700 participants with chronic heart failure and reduced ejection fraction, empagliflozin significantly reduced the risk of hospitalization for heart failure complications (13.2% vs. 18.3% for placebo) over an average of 16 months.

Empagliflozin also showed a lower incidence of serious kidney problems (1.6% vs. 3.1% for placebo), indicating its potential safety and efficacy in managing heart failure, although it was associated with a higher rate of genital tract infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug treatment with empagliflozin lowered risk for hospitalization in people with heart failure with reduced ejection fraction: plain language summary of the EMPEROR-Reduced study. Zannad, F., Macari, S.[2023]

Levosimendan, approved for clinical use since 2000, enhances heart function by sensitizing cardiac muscle to calcium and promoting blood vessel dilation, making it effective for various heart conditions like acute heart failure and cardiogenic shock.

Over the past 20 years, its clinical applications have expanded significantly, and it is currently being evaluated in the US for various cardiac and non-cardiac diseases, including a new oral formulation for managing amyotrophic lateral sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use. Papp, Z., Agostoni, P., Alvarez, J., et al.[2020]

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 rat model of chronic heart failure, torasemide significantly improved left ventricular function and survival rates compared to furosemide, indicating its superior efficacy in managing heart failure-related remodeling.

Torasemide also reduced cardiac fibrosis and levels of harmful proteins associated with heart damage, while furosemide did not show these beneficial effects, highlighting torasemide's potential in treating heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effects of torasemide and furosemide in rats with heart failure. Veeraveedu, PT., Watanabe, K., Ma, M., et al.[2018]

The article summarizes key trials related to heart failure management presented at the American Heart Association's 75th Scientific Sessions, highlighting advancements in treatment strategies.

Trials discussed include PROSPER, DIAL, and COMPANION, which focus on various aspects of heart failure such as home care monitoring, immune modulation therapy, and the impact of anemia on heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials update from the American Heart Association meeting: PROSPER, DIAL, home care monitoring trials, immune modulation therapy, COMPANION and anaemia in heart failure. Coletta, AP., Nikitin, N., Clark, AL., et al.[2019]

Heart failure remains a significant public health issue with high mortality rates, even with optimal medical treatment, highlighting the need for ongoing advancements in management strategies.

Current treatments focus on blocking harmful neurohormonal systems, using medications like diuretics, ACE inhibitors, and beta-blockers, while advanced cases may require additional therapies or surgical interventions such as heart transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Chronic heart failure--the epidemic of the 21st century]. Czuriga, I.[2014]

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 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 is an effective diuretic for treating both chronic congestive heart failure (CHF) and hypertension, showing significant improvements in body weight, pulmonary function, and CHF severity over long-term use (up to 1 year) with dosages of 5 to 20 mg/day.

In treating hypertension, low doses of torasemide (2.5 to 5 mg/day) effectively lowered diastolic blood pressure in 70-80% of patients within 8 to 12 weeks, with over 90% efficacy at higher doses, and it is well tolerated with adverse effects similar to other loop diuretics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits and risks of torasemide in congestive heart failure and essential hypertension. Brater, DC.[2018]

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.

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 ...

3.

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 ...

4.

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 ...

5.

onlinelibrary.wiley.com

onlinelibrary.wiley.com/doi/10.1002/pds.70130

Comparative Effectiveness and Safety of Torsemide Versus ...

Compared with furosemide, initiation of torsemide was associated with a slightly lower risk of a composite of all-cause mortality or heart ...

6.

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 ...

7.

karger.com

karger.com/crd/article/doi/10.1159/000546106/927883/Torsemide-in-HFrEF-Revisiting-the-Role-of-a-Potent

Torsemide in HFrEF: Revisiting the Role of a Potent Loop ...

Over a 1-year follow-up, bumetanide was associated with significantly higher risks of all-cause mortality (odds ratio [OR]: 1.28), ...