Clinical trial NCT03314025: Prophylactic Tamsulosin in Prevention of Post-operative Urinary Retention in Men After Transanal Endoscopic Microsurgery
Official title: Prophylactic Tamsulosin in Prevention of Post-operative Urinary Retention in Men After Transanal Endoscopic Microsurgery: A Multicenter Randomized, Double-blind, Placebo-controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Urinary Retention
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
First posted: 2017-10-19
Enrollment: 158
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled clinical trial
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Post-Operative Urinary Retention (POUR) (yes or no)
timeFrame: 6 hours
Secondary outcomes:
measure: Side effects of Tamsulosin Hydrochloride
timeFrame: 7 days
measure: Hospital admission
timeFrame: 24 hours
measure: Indwelling catheter
timeFrame: 1 month
measure: Recurrence
timeFrame: 24 hours after the removal of the catheter
measure: The International Prostate Symptom Score (IPSS) Score
timeFrame: 7 days
measure: Late POUR
timeFrame: Between 6 hours and 24 hours post-op
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute
state: Ontario
city: Quebec City
country: Canada
facility: CHU de Quebec - Universite Laval
state: Quebec
Study officials:
affiliation: CHU de Quebec-Universite Laval
name: Sebastien Drolet, MD FRCSC
role: PRINCIPAL_INVESTIGATOR
References:
citation: Akkoc A, Aydin C, Topaktas R, Kartalmis M, Altin S, Isen K, Metin A. Prophylactic effects of alpha-blockers, Tamsulosin and Alfuzosin, on postoperative urinary retention in male patients undergoing urologic surgery under spinal anaesthesia. Int Braz J Urol. 2016 May-Jun;42(3):578-84. doi: 10.1590/S1677-5538.IBJU.2015.0256.
citation: Bailey HR, Ferguson JA. Prevention of urinary retention by fluid restriction following anorectal operations. Dis Colon Rectum. 1976 Apr;19(3):250-2. doi: 10.1007/BF02590913.
citation: Baldini G, Bagry H, Aprikian A, Carli F. Postoperative urinary retention: anesthetic and perioperative considerations. Anesthesiology. 2009 May;110(5):1139-57. doi: 10.1097/ALN.0b013e31819f7aea.
citation: Barkin J, Diles D, Franks B, Berner T. Alpha blocker monotherapy versus combination therapy with antimuscarinics in men with persistent LUTS refractory to alpha-adrenergic treatment: patterns of persistence. Can J Urol. 2015 Aug;22(4):7914-23.
citation: Bozlu M, Ulusoy E, Doruk E, Cayan S, Canpolat B, Schellhammer PF, Akbay E. Voiding impairment after prostate biopsy: does tamsulosin treatment before biopsy decrease this morbidity? Urology. 2003 Dec;62(6):1050-3. doi: 10.1016/j.urology.2003.07.006.
citation: Buckley BS, Lapitan MC. Drugs for treatment of urinary retention after surgery in adults. Cochrane Database Syst Rev. 2010 Oct 6;(10):CD008023. doi: 10.1002/14651858.CD008023.pub2.
citation: Cataldo PA, Senagore AJ. Does alpha sympathetic blockade prevent urinary retention following anorectal surgery? Dis Colon Rectum. 1991 Dec;34(12):1113-6. doi: 10.1007/BF02050073.
citation: Chung SJ, Jung SI, Ryu JW, Hwang EC, Kwon DD, Park K, Kim JW. The preventive effect of tamsulosin on voiding dysfunction after prostate biopsy: a prospective, open-label, observational study. Int Urol Nephrol. 2015 May;47(5):711-5. doi: 10.1007/s11255-015-0955-7. Epub 2015 Mar 27.
citation: Dreijer B, Moller MH, Bartholdy J. Post-operative urinary retention in a general surgical population. Eur J Anaesthesiol. 2011 Mar;28(3):190-4. doi: 10.1097/EJA.0b013e328341ac3b.
citation: Elshaikh MA, Ulchaker JC, Reddy CA, Angermeier KW, Klein EA, Chehade N, Altman A, Ciezki JP. Prophylactic tamsulosin (Flomax) in patients undergoing prostate 125I brachytherapy for prostate carcinoma: final report of a double-blind placebo-controlled randomized study. Int J Radiat Oncol Biol Phys. 2005 May 1;62(1):164-9. doi: 10.1016/j.ijrobp.2004.09.036.
citation: Fisher E, Subramonian K, Omar MI. The role of alpha blockers prior to removal of urethral catheter for acute urinary retention in men. Cochrane Database Syst Rev. 2014 Jun 10;2014(6):CD006744. doi: 10.1002/14651858.CD006744.pub3.
citation: Goldman G, Leviav A, Mazor A, Kashtan H, Aladgem D, Greenstein A, Wiznitzer T. Alpha-adrenergic blocker for posthernioplasty urinary retention. Prevention and treatment. Arch Surg. 1988 Jan;123(1):35-6. doi: 10.1001/archsurg.1988.01400250037005.
citation: Gonullu NN, Dulger M, Utkan NZ, Canturk NZ, Alponat A. Prevention of postherniorrhaphy urinary retention with prazosin. Am Surg. 1999 Jan;65(1):55-8.
citation: Jang JH, Kang SB, Lee SM, Park JS, Kim DW, Ahn S. Randomized controlled trial of tamsulosin for prevention of acute voiding difficulty after rectal cancer surgery. World J Surg. 2012 Nov;36(11):2730-7. doi: 10.1007/s00268-012-1712-z.
citation: Jeong IG, You D, Yoon JH, Hong S, Lim JH, Hong JH, Choo MS, Ahn H, Kim CS. Impact of tamsulosin on urinary retention following early catheter removal after robot-assisted laparoscopic radical prostatectomy: a prospective randomized controlled trial. Int J Urol. 2014 Feb;21(2):164-8. doi: 10.1111/iju.12225. Epub 2013 Jul 30.
citation: Jordan CG. Post-Operative Urinary Retention. Ann Surg. 1933 Jul;98(1):125-37. doi: 10.1097/00000658-193307000-00012. No abstract available.
citation: Kapoor A. Benign prostatic hyperplasia (BPH) management in the primary care setting. Can J Urol. 2012 Oct;19 Suppl 1:10-7.
citation: Keita H, Diouf E, Tubach F, Brouwer T, Dahmani S, Mantz J, Desmonts JM. Predictive factors of early postoperative urinary retention in the postanesthesia care unit. Anesth Analg. 2005 Aug;101(2):592-596. doi: 10.1213/01.ANE.0000159165.90094.40.
citation: Lamonerie L, Marret E, Deleuze A, Lembert N, Dupont M, Bonnet F. Prevalence of postoperative bladder distension and urinary retention detected by ultrasound measurement. Br J Anaesth. 2004 Apr;92(4):544-6. doi: 10.1093/bja/aeh099. Epub 2004 Feb 20.
citation: Laliberte AS, Lebrun A, Drolet S, Bouchard P, Bouchard A. Transanal endoscopic microsurgery as an outpatient procedure is feasible and safe. Surg Endosc. 2015 Dec;29(12):3454-9. doi: 10.1007/s00464-015-4158-1. Epub 2015 Mar 24.
citation: Leventhal A, Pfau A. Pharmacologic management of postoperative overdistention of the bladder. Surg Gynecol Obstet. 1978 Mar;146(3):347-8.
citation: Livne PM, Kaplan B, Ovadia Y, Servadio C. Prevention of post-hysterectomy urinary retention by alpha-adrenergic blocker. Acta Obstet Gynecol Scand. 1983;62(4):337-40. doi: 10.3109/00016348309156234.
citation: Lose G, Lindholm P. Prophylactic phenoxybenzamine in the prevention of postoperative retention of urine after vaginal repair: a prospective randomized double-blind trial. Int J Gynaecol Obstet. 1985 Sep;23(4):315-20. doi: 10.1016/0020-7292(85)90026-8.
citation: Lowe FC. Summary of clinical experiences with tamsulosin for the treatment of benign prostatic hyperplasia. Rev Urol. 2005;7 Suppl 4(Suppl 4):S13-21.
citation: Lucas MG, Stephenson TP, Nargund V. Tamsulosin in the management of patients in acute urinary retention from benign prostatic hyperplasia. BJU Int. 2005 Feb;95(3):354-7. doi: 10.1111/j.1464-410X.2005.05299.x.
citation: Agrawal MS, Yadav A, Yadav H, Singh AK, Lavania P, Jaiman R. A prospective randomized study comparing alfuzosin and tamsulosin in the management of patients suffering from acute urinary retention caused by benign prostatic hyperplasia. Indian J Urol. 2009 Oct-Dec;25(4):474-8. doi: 10.4103/0970-1591.57917.
citation: Madani AH, Aval HB, Mokhtari G, Nasseh H, Esmaeili S, Shakiba M, Shakiba RS, Seyed Damavand SM. Effectiveness of tamsulosin in prevention of post-operative urinary retention: a randomized double-blind placebo-controlled study. Int Braz J Urol. 2014 Jan-Feb;40(1):30-6. doi: 10.1590/S1677-5538.IBJU.2014.01.05.
citation: Mason SE, Scott AJ, Mayer E, Purkayastha S. Patient-related risk factors for urinary retention following ambulatory general surgery: a systematic review and meta-analysis. Am J Surg. 2016 Jun;211(6):1126-34. doi: 10.1016/j.amjsurg.2015.04.021. Epub 2015 Jul 17.
citation: Mohammadi-Fallah M, Hamedanchi S, Tayyebi-Azar A. Preventive effect of tamsulosin on postoperative urinary retention. Korean J Urol. 2012 Jun;53(6):419-23. doi: 10.4111/kju.2012.53.6.419. Epub 2012 Jun 19.
citation: Basheer A, Alsaidi M, Schultz L, Chedid M, Abdulhak M, Seyfried D. Preventive effect of tamsulosin on postoperative urinary retention in neurosurgical patients. Surg Neurol Int. 2017 May 10;8:75. doi: 10.4103/sni.sni_5_17. eCollection 2017.
citation: Nasu K, Moriyama N, Fukasawa R, Tsujimoto G, Tanaka T, Yano J, Kawabe K. Quantification and distribution of alpha1-adrenoceptor subtype mRNAs in human proximal urethra. Br J Pharmacol. 1998 Apr;123(7):1289-93. doi: 10.1038/sj.bjp.0701731.
citation: Patel R, Fiske J, Lepor H. Tamsulosin reduces the incidence of acute urinary retention following early removal of the urinary catheter after radical retropubic prostatectomy. Urology. 2003 Aug;62(2):287-91. doi: 10.1016/s0090-4295(03)00333-9.
citation: Petersen MS, Collins DN, Selakovich WG, Finkbeiner AE. Postoperative urinary retention associated with total hip and total knee arthroplasties. Clin Orthop Relat Res. 1991 Aug;(269):102-8.
citation: Petros JG, Bradley TM. Factors influencing postoperative urinary retention in patients undergoing surgery for benign anorectal disease. Am J Surg. 1990 Apr;159(4):374-6. doi: 10.1016/s0002-9610(05)81274-7.
citation: Reitz A, Haferkamp A, Kyburz T, Knapp PA, Wefer B, Schurch B. The effect of tamsulosin on the resting tone and the contractile behaviour of the female urethra: a functional urodynamic study in healthy women. Eur Urol. 2004 Aug;46(2):235-40; discussion 240. doi: 10.1016/j.eururo.2004.04.009.
citation: Shaw MK, Pahari H. The role of peri-operative use of alpha-blocker in preventing lower urinary tract symptoms in high risk patients of urinary retention undergoing inguinal hernia repair in males above 50 years. J Indian Med Assoc. 2014 Jan;112(1):13-4, 16.
citation: Tammela T, Kontturi M, Puranen J. Prevention of postoperative urinary retention after total hip arthroplasty in male patients. Ann Chir Gynaecol. 1987;76(3):170-2.
citation: Toyonaga T, Matsushima M, Sogawa N, Jiang SF, Matsumura N, Shimojima Y, Tanaka Y, Suzuki K, Masuda J, Tanaka M. Postoperative urinary retention after surgery for benign anorectal disease: potential risk factors and strategy for prevention. Int J Colorectal Dis. 2006 Oct;21(7):676-82. doi: 10.1007/s00384-005-0077-2. Epub 2006 Mar 22.
citation: Verhamme KM, Dieleman JP, Bleumink GS, Bosch JL, Stricker BH, Sturkenboom MC. Treatment strategies, patterns of drug use and treatment discontinuation in men with LUTS suggestive of benign prostatic hyperplasia: the Triumph project. Eur Urol. 2003 Nov;44(5):539-45. doi: 10.1016/s0302-2838(03)00376-2.
citation: Wu AK, Auerbach AD, Aaronson DS. National incidence and outcomes of postoperative urinary retention in the Surgical Care Improvement Project. Am J Surg. 2012 Aug;204(2):167-71. doi: 10.1016/j.amjsurg.2011.11.012. Epub 2012 May 3.