This study has been designed to evaluate the efficacy of 24mg/48mg once daily dose of
Investigational Product [Extended release torsemide of Sarfez Pharmaceuticals Inc.] to
20mg/40mg once daily dose of generic immediate release torsemide in reducing the symptoms
of overactive bladder (OAB) in Chronic Heart Failure (CHF) patients.
Study Rationale Majority of chronic heart failure (CHF) patients are aged ≥50 and have
symptoms of overactive bladder such as micturition frequency and urgency with or without
urgency incontinence on stable dose of loop diuretics. Studies have shown that at normal
physiological filling rate, intravesicular pressure does not rise until bladder capacity
is reached. However, when the filling rate is higher than the normal physiological rate,
the intravesicular pressure rises before bladder capacity is reached. Since loop diuretic
increase filling rate, they are likely to raise intravesicular pressure much before it
reaches capacity, and hence increase urgency. Therefore, there is a need for loop
diuretic with a more gradual filling rate to alleviate loop diuretic induced exacerbation
of symptoms OAB such as urgency and frequency. The proposed study follows upon successful
clinical trial where in healthy volunteers, extended release torsemide of Sarfez
Pharmaceutical Inc. decreased peak urine volume by >30% and induced gradual diuresis,
indicating a gradual bladder filling. Therefore, this study is designed to determine if
extended release torsemide of Sarfez Pharmaceutical Inc. can improve the bladder symptoms
in heart failure patients as compared to a generic torsemide.
Patients who meet all inclusion and exclusion criteria, after obtaining written informed
consent, will be screened using a four-question bladder condition assessment tool (score
0-5) and, only patients who score ≥4 score on each of the questions (total score ≥16) and
meeting all other eligibility criteria will be enrolled in the study. The trial period
will be divided into two periods as described above and shown in study flow schema
(Figure 1). The total duration of the study would be 56 days excluding the day of
enrolment in the study. Patients will visit the Clinical Research Unit/hospital at
following schedules.
Visit 1: (Screening and Enrollment) start of study: After confirmation of eligibility and
screening, patients will be randomized, HRQL tool and BS tool will be administered,
(Baseline) and medications will be dispensed. Blood will be collected for NT-pro-BNP test
and basic metabolic panel and body weight will also be measured. 6MWT will be performed.
The other assessments will be done as mentioned in the study assessment schedule.
Pregnancy test will be done to rule out pregnancy.
Period 1: All the enrolled patients who were on stable daily dose of furosemide will be
randomized to either ERT or generic IRT. Patients who were on stable daily dose of
furosemide 40 mg will be randomized to either ERT 24 mg or generic IRT 20 mg. Similarly,
patients who were on stable daily dose of furosemide 80 mg will be randomized to either
ERT 48 mg (two 24 mg tablets) or generic IRT 40 mg (two 20mg tablets). All pre-screening
treatments will be recorded, and other concomitant medications will be continued (except
non-steroidal anti-inflammatory agents but aspirin (<100 mg per day) will be permitted,
cyclooxygenase-2 inhibitors such as Celecoxib, and allopurinol). On the same day HRQL
tool and BS tool will be administered (Baseline assessments). Trained study coordinator
will do a virtual visit on the last day of week 1, 2, and week 3 to provide and collect
daily diary and to administer BS tool in week 2 and week 3. Upon diary collection, the
study coordinator will check the diary for completion, and, if the diary is not properly
completed, the study coordinator re-educates or re-instructs the patient with proper
diary data filling procedures. Any retrospective modification or notation in the diary is
strictly prohibited.
End of Period 1 and Cross Over: At the end of Week 4 (Day 28) patients will visit the
site. After collecting daily diary from Period 1, the following assessment tools will be
administered: HRQL tool, BS tool, and PGI-C questionnaires for frequency, urgency,
urgency-incontinence, overall bladder problems, daily life and treatment satisfaction
(anchors). Blood sample will be collected for basic metabolic panel and NT-proBNP and
body weight will be measured. 6MWT will be performed along with physical examination and
vital signs assessments.
On the same day medications will be switched and drug will be dispensed. Other
assessments will be done as per the study assessment schedule.
Period 2: Trained study coordinator will do a virtual visit on the last day of week 5,
week 6, and week 7 to provide daily diary and to collect the previous week's diary as
well as to administer BS tool in week 6 and week 7. Upon diary collection, study
coordinator will check the diary for completion, and, if the diary is not properly
completed, the study coordinator will re-educate or re-instruct the patient with proper
diary data filling procedures. Any retrospective modification or notation in the diary is
strictly prohibited.
End of Study: At the end of Period 2 (Week 8, Day 56), following instruments will be
administered along with the collection of weeks 8 diary: HRQL tool, BS tool, and PGI-C
questionnaires for frequency, urgency, urgency-incontinence, overall bladder problems,
daily life and treatment satisfaction (anchors). On the same day end of study assessment
will be done as per the study assessment schedule and blood will be collected for basic
metabolic panel and NT-pro-BNP. Also, body weight will be measured. 6MWT will be
performed. End of study assessments will be performed as per study assessment schedule.
Assessment Windows The deviations for the assessment times are acceptable based on
logistical and operational considerations.