Extended Release Torsemide for Overactive Bladder in Heart Failure

Recruiting in Palo Alto (17 mi)

Overseen by Alvin Chandra

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Texas Southwestern Medical Center

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This research study is being done to compare the effectiveness two drugs: an extended release torsemide (ERT) versus generic immediate release Torsemide (IRT) in reducing the worsening of symptoms of Overactive Bladder (OAB i.e., frequency, urgency, or urgency incontinence) in patients with chronic congestive heart failure (CHF). This study will include CHF patients who experience worsening OAB) symptoms with use of a loop diuretic. The total duration of the study is about eight weeks with a total of nine visits. There will be a screening visit that lasts one to two hours. The screening visit includes history and physical exams, blood draws, and urine analysis. If eligible for the study, participants will receive either generic torsemide or extended release torsemide for the first four weeks. Participants will do a virtual research visit on week one, two and three to submit a symptom diary and answer a questionnaire about urinary symptoms. At four weeks, history and physician exam will be done and blood will be collected. Participants will be assigned to receive either extended release torsemide (if they initially received generic torsemide) and generic torsemide (if they initially received extended release torsemide) for the next four weeks. Participants will attend virtual research visits on week five, six and seven to submit a symptom diary and answer a questionnaire about urinary symptoms. At the end of the study in week eight, they will have history and physical exams and blood draws. Some risks from the study may include side effects of torsemide like acute kidney injury, fluid/electrolyte loss, hypersensitivity reactions and reversible hearing loss/tinnitus.

Do I have to stop taking my current medications for this trial?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of furosemide. If you're taking NSAIDs, Cox-2 inhibitors, or Allopurinol, you may need to switch to acetaminophen with the investigator's approval.

What data supports the idea that Extended Release Torsemide for Overactive Bladder in Heart Failure is an effective drug?

The available research does not provide specific data on the effectiveness of Extended Release Torsemide for Overactive Bladder in Heart Failure. Instead, it focuses on other drugs like fesoterodine, solifenacin, and tolterodine for treating overactive bladder. These studies show that these drugs can reduce symptoms like urinary incontinence and improve bladder function. However, there is no direct comparison or data available for Extended Release Torsemide in the context of overactive bladder in heart failure. ^{1 2 3 4 5}

What safety data exists for Extended Release Torsemide in treating heart failure?

The safety data for Extended Release Torsemide, also known as Demadex, Soaanz, or Torsemide, primarily comes from studies comparing it to furosemide in heart failure patients. These studies indicate that torsemide has a more predictable absorption and may offer better clinical outcomes, such as improved survival rates, left ventricular function, and reduced cardiac remodeling, compared to furosemide. A meta-analysis showed torsemide was associated with improved functional status and lower cardiac mortality, though no significant difference in all-cause mortality or side effects was observed between torsemide and furosemide. Pharmacodynamic studies suggest torsemide has a linear pharmacokinetic profile and a defined dose-response relationship in heart failure patients. ^{6 7 8 9 10}

Is the drug Extended Release Torsemide a promising treatment for overactive bladder in heart failure?

The provided research articles do not mention Extended Release Torsemide or its effects on overactive bladder in heart failure. Therefore, we cannot determine if it is a promising treatment based on this information. ^{4 11 12 13 14}

Research Team

Alvin Chandra

Principal Investigator

University of Texas Southwestern Medical Center

Eligibility Criteria

This trial is for people over 50 with chronic congestive heart failure (CHF) who are in NYHA functional class II-IV. They must be on a stable dose of furosemide and have an eGFR of ≥30 ml/min/1.73 m2, as well as symptoms of overactive bladder.

Inclusion Criteria

I experience symptoms of an overactive bladder.

I have moderate to severe heart condition symptoms.

I am 50 years or older with a diagnosis of heart failure.

Exclusion Criteria

Urinalysis containing white blood cells indicative of urinary tract infection

I have liver cirrhosis.

Any known allergy to diuretics or sulphonamide-derived compounds

Treatment Details

Interventions

• Extended Release Torsemide (Diuretic)

Trial Overview The study compares extended release torsemide (ERT) to immediate release Torsemide (IRT) for reducing worsening symptoms of Overactive Bladder in CHF patients. It's an eight-week study with nine visits including physical exams, blood tests, and symptom diaries.

Participant Groups

Group I: Investigational product Experimental Treatment 2 Interventions

Extended release torsemide and immediate release torsemide placebo

Group II: Control product Active Control 2 Interventions

Immediate release torsemide and extended release torsemide placebo

Extended Release Torsemide is already approved in United States for the following indications:

🇺🇸 Approved in United States as Demadex for:

• Edema associated with congestive heart failure
• Edema associated with renal disease
• Edema associated with hepatic disease
• Hypertension

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cardiometabolic Research Unit Dallas, TX

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1102

Patients Recruited

1,077,000+

Sarfez Pharmaceuticals, Inc.

Lead Sponsor

Trials

6

Patients Recruited

100+

References

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

Flexible-dose fesoterodine in elderly adults with overactive bladder: results of the randomized, double-blind, placebo-controlled study of fesoterodine in an aging population trial. [2015] To assess the efficacy and safety of flexible-dose fesoterodine in elderly adults with overactive bladder (OAB).

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

Effectiveness of Solifenacin and Trospium for Managing of Severe Symptoms of Overactive Bladder in Patients With Benign Prostatic Hyperplasia. [2022] This research is aimed to study the possibility of management of severe symptoms of overactive bladder (OAB) with solifenacin and trospium in patients who receive treatment with tamsulosin due to benign prostatic hyperplasia (BPH). The 338 men more than 50 years old (average age 58.4 years) diagnosed with BPH and severe symptoms of OAB were enrolled in the study. Over three episodes of urinary incontinence per day (registration according to bladder diaries), INTERNATIONAL PROSTATE SYMPTOM SCORE: over 19, OAB-V8 questionnaire score over 32, and urodynamic disorders diagnosed using cystometry and uroflowmetry were taken as a criterion of severe symptoms of OAB. Patients of the main group during 2 months received treatment with daily combination of solifenacin 5 mg and trospium 5 mg simultaneously with tamsulosin 0.4 mg. Patients of the control group were treated only with tamsulosin. First endpoint is a quantitative assessment of patients with BPH having severe symptoms of OAB. Second endpoint is a state of the patients' lower urinary tract after the treatment. In the main group, most of urodynamic indices normalized significantly. Number of episodes of incontinence reduced from middle level 3.4 (0.8) per day to 0.9 (0.7) per day. In the control group changes of urodynamic indices were not significant. Quantity of side effects did not exceed the level which is common for antimuscarinic monotherapy. Therefore, percentage of patients with severe symptoms of OAB is not less than 44% of all cases of prostatic hyperplasia accompanied by OAB symptoms. Combination of trospium and solifenacin in standard doses is an efficient and safe method of management of severe symptoms of OAB in the course of the treatment of with tamsulosin in patients more than 50 years of age.

3. England pubmed.ncbi.nlm.nih.gov

Long-term safety, tolerability, and efficacy of fesoterodine treatment in men and women with overactive bladder symptoms. [2012] To evaluate long-term safety, tolerability, and efficacy of fesoterodine for men and women with overactive bladder (OAB) symptoms.

4. England pubmed.ncbi.nlm.nih.gov

Characteristics of antimuscarinic responders versus suboptimal responders in a randomized clinical trial of patients with overactive bladder symptoms. [2018] To assess the characteristics of tolterodine extended-release (ER) 4 mg responders and suboptimal responders (≤50% decrease in UUI episodes/24 h) among patients with overactive bladder (OAB), including urgency urinary incontinence (UUI), and identify predictors of a >50% UUI response with fesoterodine 8 mg in tolterodine suboptimal responders.

5. Spain pubmed.ncbi.nlm.nih.gov

Use of health care resources and associated costs in non-institutionalized vulnerable elders with overactive bladder treated with antimuscarinic agents in the usual medical practice. [2018] To evaluate the use of resources and health costs in vulnerable elderly institutionalized patients with overactive bladder (OAB) treated with fesoterodine, tolterodine or solifenacin in routine medical practice.

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

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure. [2019] Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide.

7. England pubmed.ncbi.nlm.nih.gov

Comparative effects of torasemide and furosemide in rats with heart failure. [2018] It has been reported that torasemide but not furosemide, may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. We therefore compared the therapeutic effects of torasemide, a long-acting loop diuretic, and furosemide, a short-acting one, on the progression of LV remodeling in a rat model of chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM). CHF was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide, or vehicle. We investigated the effects on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in EAM rats. Diuresis was increased dose dependently by both torasemide and furosemide, showed an equipotent natriuretic effect. The urinary potassium excretion was significantly increased with furosemide in comparison to torasemide. Myocardial functional parameters were significantly improved by torasemide. Conversely, these parameters did not change in rats receiving furosemide. Torasemide suppressed LV fibrosis, myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase and improved survival rate to the control level, but furosemide did not. Moreover, both pharmacological interventions significantly elevated plasma angiotensin II and decreased atrial natriuretic peptide in a dose-dependent manner. Our results demonstrate that compared with furosemide, torasemide treatment significantly improved survival rate, LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.

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

Meta-Analysis Comparing Torsemide Versus Furosemide in Patients With Heart Failure. [2020] Although torsemide's oral bioavailability and half-life theoretically render it a more efficient diuretic than furosemide, the clinical outcomes of torsemide compared with furosemide remain unclear. We performed a systematic review and meta-analysis, including all published studies that compared torsemide and furosemide use in heart failure patients from January 1996 through August 2019. Nineteen studies (9 randomized control trials [RCTs] and 10 observational studies) with a total of 19,280 patients were included. During a mean follow-up duration of 15 months, torsemide was associated with a numerically lower risk of hospitalization due to heart failure (10.6% vs 18.4%; odds ratio [OR] 0.72, 95% confidence interval [CI] [0.51, 1.03], p = 0.07, I2 = 18%; number needed to treat [NNT] = 23) compared with furosemide. Torsemide was associated with statistically significant more improvement in functional status from New York Heart Association (NYHA) class III/IV to I/II (72.5% vs 58%; OR 2.32, 95% CI (1.32, 4.1), p = 0.004, I2 = 27%; NNT = 5) and lower risk of cardiac mortality (1.5% vs 4.4%; OR 0.37, 95% CI (0.20, 0.66), p <0.001, I2 = 0%, NNT = 40) compared with furosemide. However, there was no difference in all-cause mortality or medication side effects between the 2 groups. In conclusion, compared with furosemide, torsemide use was associated with significant more improvement in functional status and lower cardiac mortality; and numerically fewer hospitalizations in patients with heart failure.

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

Effects of increased dose of diuretics on symptoms, weight, 6-minute walk distance, and echocardiographic measurements of left ventricular systolic and diastolic function in 51 patients with symptomatic heart failure caused by reduced left ventricular ejection fraction treated with beta blockers and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. [2013] We investigated in 51 consecutive outpatients with symptomatic congestive heart failure caused by abnormal left ventricular (LV) ejection fraction treated with furosemide or torsemide (10% also with metolazone), beta blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, 55% with spironolactone, and 18% with digoxin, the effects of doubling the dose of furosemide, torsemide, and metolazone on symptoms, weight, 6-minute walk distance, and echocardiographic measurements of LV systolic and diastolic function at 24 ± 6 days follow-up. At follow-up, the weight decreased from 70 ± 6 kg to 65 ± 6 kg (P

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

The pharmacodynamics of torsemide in patients with congestive heart failure. [2019] The pharmacodynamics of torsemide (a new loop diuretic of the pyridine sulfonylurea class) was studied in 16 subjects who had compensated congestive heart failure and had been receiving stable diuretic therapy. Oral doses of 50, 100, and 200 mg were studied by use of a randomized crossover design. The results of this study show that the pharmacokinetics of torsemide is linear up to at least a dose of 200 mg in patients with congestive heart failure. Approximately 20% of each of the three doses was excreted unchanged, consistent with previous findings in healthy volunteers. A hyperbolic relationship between diuretic effect and drug excretion rate was defined. The maximum urinary sodium excretion rate attained was about 0.6 mEq/min, which is about 20% of that in healthy subjects, indicating diuretic resistance in these patients. Although there was no saturation of the urinary excretory pathway with doses as high as 200 mg, the upper plateau of the dose-response curve was reached with doses of 50 mg, indicating that this dose represents a ceiling dose in patients with New York Heart Association class II and III congestive heart failure.

11. Australia pubmed.ncbi.nlm.nih.gov

Long-term safety, tolerability and efficacy of extended-release tolterodine in the treatment of overactive bladder in Japanese patients. [2015] To evaluate the long-term safety, tolerability and efficacy of extended-release (ER) tolterodine in Japanese patients completing 12-week treatment in a randomized, double-blind trial comparing tolterodine ER 4 mg once daily, oxybutynin 3 mg three times daily or placebo in patients with overactive bladder.

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

Oxybutynin extended-release: a review of its use in the management of overactive bladder. [2019] The OROS-based oxybutynin extended-release (ER) formulation (Lyrinel XL; Ditropan XL) represents a new form of oral delivery for oxybutynin, a muscarinic receptor antagonist used in the treatment of overactive bladder (OAB). The release of oxybutynin from oxybutynin ER occurs in a sustained manner, resulting in a smoother plasma concentration-time profile and a lower maximum plasma concentration than those seen with oxybutynin immediate-release (IR). The ER formulation has been developed with the aim of improving the tolerability of oxybutynin therapy and facilitating once-daily administration. Moreover, oxybutynin ER offers greater flexibility in dosage (5-30 mg/day) than the other available treatment options. At dosages of 5-30 mg once daily, oxybutynin ER produced significant decreases from baseline in weekly urinary urge incontinence in patients with OAB. In addition, there were significant decreases in weekly total incontinence episodes and micturition frequency. In two randomised, double-blind studies in patients with OAB, the improvement in all the symptoms with once-daily oxybutynin ER 5-30 mg/day was similar to that produced by oxybutynin IR 5-20 mg/day given one to four times daily. Once-daily oxybutynin ER 10 mg was superior to tolterodine IR 4 mg/day given as two daily doses and as effective as once-daily tolterodine ER 4 mg/day in decreasing urinary incontinence; the decreases in micturition frequency with oxybutynin ER were significantly greater than those seen with either of tolterodine formulations. Oxybutynin ER was well tolerated in all the trials, with adverse events usually being mild to moderate and transient. In direct comparisons, the overall tolerability profile of oxybutynin ER was better than that of oxybutynin IR. Oxybutynin ER was similar to tolterodine (IR and ER) with respect to the incidence of clinically important dry mouth. A large 12-month tolerability study demonstrated no significant risks associated with the long-term use of oxybutynin ER. A few noncomparative studies have shown promising results with oxybutynin ER in the treatment of adult and paediatric patients with neurogenic bladder dysfunction secondary to neuronal injury. Long- and short-term studies have reported significant improvements in health-related quality of life with oxybutynin ER therapy. In addition, pharmacoeconomic studies have suggested that oxybutynin ER is more cost effective than oxybutynin IR and at least as cost effective as tolterodine IR. In conclusion, oxybutynin ER shows excellent efficacy in the treatment of symptoms associated with OAB in adults and the elderly with a good tolerability profile over a prolonged period of use (12 months). The ER formulation of oxybutynin provides a smooth plasma concentration profile over the 24-hour dosage interval, facilitating once-daily administration. Hence, given its overall efficacy/tolerability profile and dosage flexibility, oxybutynin ER provides an excellent treatment option in the first-line pharmacotherapy of OAB.

13. England pubmed.ncbi.nlm.nih.gov

Onset of efficacy of tolterodine extended release in patients with overactive bladder. [2019] To assess the onset of efficacy of tolterodine extended release (ER) in patients with overactive bladder (OAB).

14. Australia pubmed.ncbi.nlm.nih.gov

Efficacy of extended-release tolterodine for the treatment of neurogenic detrusor overactivity and/or low-compliance bladder. [2022] To evaluate the efficacy of extended-release (ER) tolterodine 4mg/day for the treatment of neurogenic detrusor overactivity (NDO) and/or low-compliance bladder by assessing urodynamic parameters.