Clinical trial NCT02262936: Comparison Between Desmopressin and Fesoterodine for Treatment of Night Time Voiding in Women Aged 65 and Older
Official title: A Randomized Double-blinded Trial Comparing DEsmopressin to FEsoterodine in the Treatment of Severe Nocturia in Women Aged 65 and olDer: The DEFEND Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Nocturia
Keywords: Aged
Deamino Arginine Vasopressin
Fesoterodine
Randomized Controlled Trial
Lead sponsor: Mount Sinai Hospital, Canada
Sponsor class: OTHER
Collaborators: name: Baycrest
name: The Physicians' Services Incorporated Foundation
First posted: 2014-10-13
Enrollment: 4
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Nocturia, or voiding at night, is an extremely troublesome symptom which is highly prevalent in the elderly. Desmopressin is a treatment for nocturia but it can result in hyponatremia (low blood sodium), particularly in those aged 65 and older. Fesoterodine is used for the treatment of overactive bladder (OAB). Recent trials showed Fesoterodine was effective in reducing nocturia. This study aims to answer the following: In women 65 and older with severe nocturia, is Fesoterodine more effective than Desmopressin in reducing the number of night time voids? Does Fesoterodine have a better side effect profile compared to Desmopressin?

The study design is a 12 week randomized double-blinded trial of Fesoterodine and Desmopressin in the treatment of severe nocturia in women aged 65 and older. This will be conducted at the Urogynecology Unit at Mount Sinai Hospital (MSH) and Baycrest. A 3 day voiding diary and Nocturia, Nocturnal Enuresis and Sleep-interruption Questionnaire (NNES-Q) will be completed at baseline and at week 12. The primary outcome will be the number of night time voids in the Fesoterodine group compared to the Desmopressin group, 12 weeks after starting treatment. Secondary outcomes include changes in the NNES-Q scores and the safety of each medication.

This study is expected to show that, in women 65 and older with severe nocturia, Fesoterodine will be more effective in reducing the number of night time voids, reducing the volume of voided urine, increasing the duration of sleep prior to first nocturnal void and improving quality of life relative to Desmopressin. Fesoterodine will also be better tolerated, with fewer significant adverse events, relative to Desmopressin.

Detailed description: This study will include female patients 65 years and older from the Urogynecology Units at Mount Sinai Hospital (MSH) and Baycrest. It will be a 12 week prospective, randomized double-blind trial comparing treatment of nocturia using Fesoterodine and Desmopressin. Patients who agree to participate in the study will receive a starting dose of either Fesoterodine 4mg tablet at bedtime or Desmopressin 0.1mg tablet at bedtime. After 4 weeks, if patients have had minimal improvement in their symptoms and are not significantly affected by side effects, patients will have the option of increasing the dose of their medication to 8mg of Fesoterodine or 0.2mg of Desmopressin. This decision will be made by the patient and physician together.

Patients will undergo block randomization by pharmacy. All patients and investigators will be blinded to the treatment group. Patients will be followed for 12 weeks, with visits at 4 and 12 weeks. Patients will also have urine cultures and uroflowmetry with measurement of post-void residuals at these visits, as per clinic standard of care. Venipuncture to monitor electrolyte levels will be done at baseline, 1 week after randomization and then monthly until the end of the study. If patients choose to increase their dose at the 4 week visit, electrolyte levels will be repeated one week after the dose adjustment and then monthly until the end of the study. The last follow up is at 12 weeks, when a 3 day voiding diary and the NNES-Q will be collected.

Eligibility criteria: Inclusion Criteria:

* Menopausal female patients aged 65 years and older
* Patients with severe nocturia, defined as waking to void 3 or more times at night due to an urge to void
* Patients capable of understanding and having signed the consent form after full discussion of the research, nature of the treatment, its risks and benefits

Exclusion Criteria:

* Urinary tract infection or chronic inflammation such as interstitial cystitis and bladder stones
* Urinary and gastric retention
* Narrow-angle glaucoma
* von Willebrand's disease
* Chronic severe constipation or history of gastrointestinal obstructive disease
* Untreated congestive heart failure and venous insufficiency
* Untreated hypertension or tachycardia
* Untreated renal or liver disease
* Untreated diabetes mellitus or insipidus
* Unexplained and untreated electrolyte disturbances
* Any clinical condition which in the opinion of the investigator would not allow safe completion of the study
* Current use of diuretics with untreated electrolyte disturbances
* Patients taking drugs known to be strong CYP3A4 inhibitors (protease inhibitors, ketoconazole, clarithromycin) or strong CYP3A4 inducers (carbamazepine, phenytoin, St. John's Wort) used on a regular basis
* Patients taking anticholinergic or antispasmodic medications who did not comply with a minimum 14 days washout period
* Previous failed therapy with Fesoterodine or Desmopressin
* Hypersensitivity or intolerance to Fesoterodine or Desmopressin
* Hypersensitivity to soya, peanuts or lactose
* Clinically significant outlet obstruction as determined by the investigator
* Patients with Post Void Residual (PVR) \> 100 ml
* Patients with Mini-Mental State Exam (MMSE) \<24

Primary outcomes:
measure: Number of night time voids
timeFrame: 18 months
Secondary outcomes:
measure: Adverse event profile
timeFrame: 18 months
measure: Quality of life
timeFrame: 18 months
measure: Nocturnal voided volume
timeFrame: 18 months
measure: Time to first nocturnal void
timeFrame: 18 months
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Mount Sinai Hospital
state: Ontario
Study officials:
affiliation: MOUNT SINAI HOSPITAL
name: Harold P Drutz, MD
role: PRINCIPAL_INVESTIGATOR
References: