Prophylactic Tamsulosin in Prevention of Post-operative Urinary Retention in Men After Transanal Endoscopic Microsurgery
Prophylactic Tamsulosin in Prevention of Post-operative Urinary Retention in Men After Transanal Endoscopic Microsurgery
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.
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 three first participating Canadian
 centers, which translates into a mean of 12 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.
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)