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Prophylactic Tamsulosin in Prevention of Post-operative Urinary Retention in Men After Transanal Endoscopic Microsurgery

Phase 2
Conditions
Urinary Retention
Interventions
Drug: Placebo oral capsule
Device: Foley catheter
Registration Number
NCT03314025
Lead Sponsor
CHU de Quebec-Universite Laval
Brief Summary

Post-operative urinary retention (POUR) is a frequent complication reported as ranging from 10 to 55% in the literature. In a recent retrospective study from Laliberte et al in Quebec City, we observed that 19% of the patients operated using transanal endoscopic microsurgery (TEM) had a post-operative urinary retention (POUR). Factors related to the patient, the tumor and the surgery were not observed to be associated risk factors. Tamsulosin has been shown as an effective preventive agent of POUR for certain ano-rectal and inguinal surgeries. The efficacy of this prophylactic therapy in transanal endoscopic microsurgery has not been studied yet and is unclear considering the particularities of this procedure. TEM uses a rigid proctoscope of four centimeters of diameter and creates a continuous pneumorectum (insufflation of the rectum during all the procedure). We think that these two elements, which cause local inflammation, may be part of the reason explaining the high incidence of post-operative urinary retention after TEM procedures. The objective of our multicenter clinical trial is to evaluate the effect of perioperative tamsulosin for the reduction of POUR in men, as well as the impact on the interventions and hospital admissions related to this complication.

Detailed Description

We are conducting a feasibility study (Vanguard phase) with three Canadian centers :

1. CHU de Quebec - Laval University, Quebec City, Quebec, Canada

2. St-Paul's Hospital, Vancouver, British-Columbia, Canada

3. Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Other Canadian centers will be offered to join our study if the Vanguard phase demonstrates the feasibility of this clinical trial.

Large scale study

We anticipate the detection of a 15% absolute risk reduction of POUR in the Experimental group in comparison with the Placebo group. To detect a 15% reduction of POUR in the Experimental group (10% anticipated) in comparison with the Placebo group (25% anticipated) and to assure a study power of 80% with a unilateral Chi2 and a significance level of 5%, we need 158 patients in total; 79 in each group.

Feasibility study (Vanguard phase)

We expect at least a 60% recruitment rate throughout the two first participating Canadian centers, which translates into a mean of 8 patients recruited each month overall. Regarding the medication adherence, two studies that evaluated the use patterns and adherence to medications for lower urinary tract symptoms suggestive of benign prostatic hyperplasia found an adherence of 67% to 89%, with a mean of 78%. Based on these two studies, we expect that the patients will at least take 80% of the medication at study. To detect an 80% medication adherence with a 95% confidence interval, we need 62 enrolled patients.

The research pharmacy at the CHU de Quebec - Laval University will be responsible for preparing the study drug. The active medication or the placebo (sugar) will be encapsulated using identical capsules. The research pharmacy at the coordinating center will provide the study drug and the placebo to the other participating centers. There will be a quality control of the capsules; a temperature monitor will be in the boxes sent to the other centers and a control on the expiration date will be made. The capsules that are not used will be destroyed at each center. The randomization will be kept at the CHU de Quebec - Laval University research center. Patients will be stratified by center.

The patients are asked to report any potential adverse effect and our data safety monitoring board will meet annually to assess these or sooner if any adverse effect is serious.

We justify the duration of the intervention by the time needed to reach a steady state, which is estimated to be 4 to 5 days. The 7-day therapy is also based on the study from Patel et al, which showed a significant reduction of acute urinary retention with a 7-day intake of tamsulosin. It is the common and recommended dose used in other patient population.

Data collection

Patients will be identified by a study number in the study database. A master list of participants linking their study number with their medical record number will be kept in the computer of the PI at every research center participating in the study, and will be password protected. Data will be collected prospectively at the bedside during the study period.

Statistical analysis

First, a descriptive analysis of the population at study will be performed for socio- demographic, anthropometric and clinical characteristics. The means, standard deviations, medians and interquartile ranges will be presented as continuous numerical variables, while the frequencies and percentages will be determined for categorical variables. In the large-scale study, a Chi-square test or Fisher Exact test, if appropriate, will be used for the analysis of the primary endpoint, which is the comparison of the rate of POUR in the Experimental group with the rate of POUR in the Placebo group. This same test will also be helpful in the analysis of the secondary endpoints. If the patient doesn't take all of his medication or his surgery is cancelled he will still be included, since this will be an intention-to-treat analysis. Sub-group analyses will be performed to evaluate the impact of the tumour's characteristics, the duration of the surgery, the volume of intravenous fluids received during the intervention, the type of anaesthesia and the International Prostate Symptom Score (IPSS).

Potential conflicts of interest

This is an investigator-led study that is independent and not sponsored by the industry. The study is funded through local funds (CHU de Quebec - Laval University, Department of Surgery) as well as from in-kind funding of the institution.

Recruitment & Eligibility

Status
UNKNOWN
Sex
Male
Target Recruitment
158
Inclusion Criteria
  • Male patients of 18 years and older that are scheduled for a TEM resection during the study period.
Exclusion Criteria
  • Patient already taking an alpha1-adrenergic blocking agent Flomax® (Tamsulosin), Cardura® (Doxazosin), Hytrin® (Terazosine) Rapaflo® (Silodosin), Xatral® (Alfuzosin), Minipress® (Prazosin)
  • Patient having an indwelling bladder catheter
  • Allergy or hypersensibility to any alpha1-adrenergic blocking agent
  • Patient taking one of the following:

Anti-retroviral therapy, Antifungal drug, Clarithromycin, Erythromycin, Paroxetine, Terbinafine, Cimetidine, Warfarin, Sildenafil, Tadalafil, Vardenafil (these drugs have possible interactions with the study drug)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
TamsulosinFoley catheterThe patients in the Experimental group will receive Tamsulosin Hydrochloride 0.4 MG (milligrams) once a day for 5 days before the surgery, one capsule on the day of the surgery and one on the day after. The intervention will consist of a total of 7 capsules
PlaceboPlacebo oral capsuleThe patients in the Placebo group will receive a placebo oral capsule (sugar) once a day for 5 days before the surgery, one capsule on the day of the surgery and one on the day after. The intervention will consist of a total of 7 capsules
PlaceboFoley catheterThe patients in the Placebo group will receive a placebo oral capsule (sugar) once a day for 5 days before the surgery, one capsule on the day of the surgery and one on the day after. The intervention will consist of a total of 7 capsules
TamsulosinTamsulosin Hydrochloride 0.4 MGThe patients in the Experimental group will receive Tamsulosin Hydrochloride 0.4 MG (milligrams) once a day for 5 days before the surgery, one capsule on the day of the surgery and one on the day after. The intervention will consist of a total of 7 capsules
Primary Outcome Measures
NameTimeMethod
Post-Operative Urinary Retention (POUR) (yes or no)6 hours

The absence of natural voiding after a surgery needing an intervention as a Foley catheter or a catheterization. If the patient needs this intervention, he will be stated to have had a POUR.

Secondary Outcome Measures
NameTimeMethod
Late POURBetween 6 hours and 24 hours post-op

Late post-operative urinary retention

Indwelling catheter1 month

Duration of the indwelling catheter (24-48 hours vs more than 48 hours)

The International Prostate Symptom Score (IPSS) Score7 days

The standardized questionnaire will be submitted to the patients before and after the prophylactic therapy. The score is out of 35.

Score Correlation

0-7 Mildly symptomatic

8-19 Moderately symptomatic

20-35 Severely symptomatic

Side effects of Tamsulosin Hydrochloride7 days

Every potential side effect will be reported

Recurrence24 hours after the removal of the catheter

Recurrence of urinary retention after catheter removal

Hospital admission24 hours

Every admission related to the primary outcome

Trial Locations

Locations (3)

Ottawa Hospital Research Institute

🇨🇦

Ottawa, Ontario, Canada

St. Paul's Hospital

🇨🇦

Vancouver, British Columbia, Canada

CHU de Quebec - Universite Laval

🇨🇦

Quebec City, Quebec, Canada

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