Comparative Study of the Efficacy and Safety of Muscarinic M3 Receptors Antagonists in the Treatment of Neurogenic Detrusor Overactivity

• ClinicalTrials.gov Identifier: NCT00800462
• Recruitment Status: Completed
• First Posted: December 2, 2008
• Last Update Posted: April 8, 2013
• Sponsor: Toronto Rehabilitation Institute
• Collaborator: Ontario Neurotrauma Foundation
• Information provided by (Responsible Party): Magdy Hassouna, Toronto Rehabilitation Institute

Study Description

Brief Summary:

This is a phase IV, double-blind, multicenter, randomized trial evaluating the efficacy and safety of two M3 receptors antagonists (Trospium Chloride and Darifenacin Hydrobromide) with one standard drug (Oxybutynin Chloride) for treatment of overactive bladder in individuals with spinal cord injury.

Condition or disease	Intervention/treatment	Phase
Spinal Cord Injury; Neurogenic Detrusor Overactivity	Drug: Oxybutynin Cl; Drug: Trospium Cl; Drug: Darifenacin Hydrogen Bromide (HBr)	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Comparative Study of the Efficacy and Safety of Muscarinic M3 Receptors Antagonists in the Treatment of Neurogenic Detrusor Overactivity
• Study Start Date: March 2008
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: December 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Oxybutynin Cl	Drug: Oxybutynin Cl; 15 mg qd for 3 months; Other Name: Uromax
Active Comparator: Trospium Cl	Drug: Trospium Cl; 20mg bid for 3 months; Other Name: Trosec
Active Comparator: Darifenacin Hydrogren Bromide (HBr)	Drug: Darifenacin Hydrogen Bromide (HBr); 15 mg qd for 3 months; Other Name: Enablex

Outcome Measures

Primary Outcome Measures :

1. Frequency of Incontinence Episodes [ Time Frame: 3 days ]
2. Adverse Event Reporting [ Time Frame: Each Study Visit and Follow-up Phone Call ]

Secondary Outcome Measures :

1. Urodynamic Study [ Time Frame: Baseline and 3 months ]
2. Questionnaires [ Time Frame: Monthly ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Male or female patients, between 18 and 75 years of age. Female patients of childbearing potential* must have a negative urine pregnancy test result on the day of Screening Visit and practice a reliable method of contraception**

   *A female is considered of childbearing potential unless she is:

   • Postmenopausal for at least 12 months prior to study drug administration;
   • Without a uterus and/or both ovaries; or

   • Has been surgically sterilized for at least 6 months prior to study drug administration.

     **Reliable methods of contraception include:

   • Hormonal methods or intrauterine device in use at least 30 days prior to study drug administration;
   • Barrier methods plus spermicidal in use at least 14 days prior to study drug administration; or
   • Sexual abstinence as a lifestyle.

2. Patients with a neurogenic bladder and detrusor overactivity secondary to a spinal cord injury.

   • Patients with urinary incontinence (minimum of one occurrence per day) despite current treatment. [NOTE: Bladder emptying may be accomplished with straining, intermittent catheterization (IC), spontaneous micturition or leakage episodes.]
3. Patients with serum creatinine within normal limits and normal renal function
4. Patients on a stable dose (minimum one month) of concomitant medication for Neurogenic detrusor overactivity
5. Patients must have adequate cognitive function to understand the requirements of the study, including completing questionnaires and signing a written Informed Consent.

Exclusion Criteria:

1. Female patients who are pregnant (positive urine pregnancy test), planning to become pregnant during the study period, breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control.
2. Patients with a history of transurethral sphincterotomy, bladder neck or prostatic resection, previous bladder surgery including myomectomy or augmentation cystoplasty.
3. Patients with chronic indwelling catheters.
4. Patients with, in the opinion of the Investigator, unstable or stable multiple sclerosis.
5. Patients with known, uncontrolled systemic disease.
6. Patients with evidence of recent alcohol/drug abuse.
7. Patients with urinary retention, gastrointestinal obstructive disorders or uncontrolled narrow-angle glaucoma.
8. Patients with contraindications to Trosec™, Enablex™ and Uromax®.
9. Patients who, in the opinion of the Investigator, have a significant condition or situation that may put the patient at significant risk, confound the study results, or interfere significantly with the patient's participation in the study.
10. Patients with a history of poor cooperation, non-compliance, or unreliability.
11. Patients currently participating in an investigational drug study or who have participated in an investigational drug study within 30 days of the Screening Visit.
12. Patients administered anticholinergics and/or antispasmodic drugs during the course of the study.
13. Patient with hepatic insufficiency.
14. Patient has been administered intravesical botulinum toxin within 6 months prior to the Screening Visit and/or is expected to receive intravesical botulinum toxin during the course of the study.
15. Patient has any medical condition that would interfere with the interpretation of the study results or the conduct of the study.

Contacts and Locations

Locations

Canada, Manitoba

University of Manitoba, Health Sciences Centre

Winnipeg, Manitoba, Canada, R3A1R9

Canada, Ontario

Toronto Rehabilitation Institute, Lyndhurst Centre

Toronto, Ontario, Canada, M4G 3V9

Sponsors and Collaborators

Toronto Rehabilitation Institute

Ontario Neurotrauma Foundation

Investigators

• Principal Investigator: Magdy Hassouna, MD; Toronto Rehabilitation Institute

More Information

Additional Information:

Ontario Neurotrauma Foundation 

• Responsible Party: Magdy Hassouna, MD PhD FRCSC FACS, Toronto Rehabilitation Institute
• ClinicalTrials.gov Identifier: NCT00800462
• Other Study ID Numbers: 2007-SCI-M3-488
• First Posted: December 2, 2008
• Last Update Posted: April 8, 2013
• Last Verified: April 2013

Additional relevant MeSH terms:

Spinal Cord Injuries; Urinary Bladder, Overactive; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Urinary Bladder Diseases; Urologic Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Bromides; Oxybutynin; Darifenacin; Anticonvulsants; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents