Torsemide for Heart Failure

(EXTOR-HF Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Nayle A Ancares, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Waitlist Available

Sponsor: Sarfez Pharmaceuticals, Inc.

Must be taking: Loop diuretics

Disqualifiers: Recent MI, Stroke, AKI, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

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 participants' loop diuretics will be replaced by the equivalent dose of immediate release/extended release torsemide for one week. After a one week period, they will report to the site and will receive a single dose of either immediate release or extended release Torsemide. The sodium excretion will be measured for six hours after dosing and for an additional six hours after a high salt lunch.

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.

Is torsemide safe for human use?

Torsemide is generally well tolerated in humans, with common side effects similar to other diuretics, such as dizziness, headache, and gastrointestinal issues. It is considered safe for long-term use at dosages up to 20 mg/day, with adverse effects rarely requiring discontinuation. ^{1 2 3 4 5}

What makes the drug Torsemide unique for treating heart failure?

Torsemide is a diuretic (a drug that helps remove excess fluid from the body) used to treat heart failure by reducing fluid retention, which can help alleviate symptoms like swelling and shortness of breath. It is unique because it is often more potent and has a longer duration of action compared to other diuretics, which may lead to more effective fluid management in heart failure patients. ^{6 7 8 9 10}

Research Team

Sophia Shah, MD

Principal Investigator

Safez Pharmaceuticals

Nayle A Ancares, MD

Principal Investigator

Future Life Clinical Trials

Eligibility Criteria

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 have been taking water pills for the last 30 days.

I don't expect to change my heart failure medications soon.

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.

Trial Timeline

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

Treatment Details

Interventions

• Torsemide (Diuretic)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. New Zealand pubmed.ncbi.nlm.nih.gov

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

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Comparative effects of torasemide and furosemide in rats with heart failure. [2018]

6. England 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. [2023]

7. England 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. [2019]

8. Hungary pubmed.ncbi.nlm.nih.gov

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

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

Disopyramide-induced ventricular tachycardia. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use. [2020]