Study to Prevent Postoperative Urinary Retention (STOP-POUR)

Randomized, Quadruple Blinded, Placebo Controlled, Multi-centered Trial Investigating Prophylactic Tamsulosin in Prevention of Postoperative Urinary Retention in Men After Endoscopic Total Extraperitoneal Inguinal Hernia Repair

Post-operative urinary retention (POUR) is a common complication after inguinal hernia repair with a reported incidence up 34%. It can be described as the inability to initiate urination or properly empty one's bladder following surgery. It is usually self-limited, but it requires the use of catheterization to empty the bladder in order to prevent further injury to the bladder or kidneys and to relief the discomfort of a full bladder. Tamsulosin is a medication that is commonly used in men with urinary symptoms related to an enlarged prostate. There is some evidence to suggest that it may also potentially be beneficial for preventing post-operative urinary retention.

The purpose of this study is to determine if tamsulosin ("TAMSULOSIN Mepha Ret Depocaps 0.4 mg") is effective in preventing post-operative urinary retention following endoscopic total extraperitoneal inguinal hernia repair and its impact on hospital length of stay.

Study Overview

• Status: Recruiting
• Conditions: Inguinal Hernia; Urinary Retention
• Intervention / Treatment: Drug: TAMSULOSIN Mepha Ret Depocaps 0.4 mg; Drug: Control Intervention

Detailed Description

In this RCT subjects are randomly and parallel assigned to one of two groups: one (the experimental group) receiving "Tamsulosin 0.4 mg"/ day, 5 days prior to the day of laparoscopic inguinal hernia repair surgery, at the day of surgery and for 1 day following surgery. (5+1+1), and the other (the control group) receiving one placebo capsule matching the active study drug per day from 5 days prior to the day of surgery, at the day of surgery and for 1 day following surgery. (5+1+1). There will be effective (concealed) randomization of the subjects to the intervention/control groups (to eliminate selection bias and minimize confounding variables). Both groups will be treated identically in all respects except for the intervention being tested and to this end patients, investigators, care providers and outcomes assessors will be blinded to which group an individual is assigned. Group assignment will be performed using a covariate-adaptive allocation procedure to provide a balance for selected covariates (Site, IPSS-Score, Age, "uni- or bilateral surgery" and "history of prostate or bladder surgery". To achieve that; Minimization, first described by Taves [and expanded by Pocock and Simon [the most commonly used covariate-adaptive randomization method will be applied. It achieves the balance in treatment assignments across factor levels by choosing the allocation for the new subject that would lead to the smallest degree of imbalance possible across the set of his baseline characteristics. The two groups are then followed up to 3 days after surgery to see if there are any differences between them in primary and secondary outcomes. Patients are analyzed within the group to which they were allocated, irrespective of whether they experienced the intended intervention (intention to treat analysis). This RCT is designed as a superiority trial and aims to demonstrate the superiority of Tamsulosin in prevention of POUR compared to placebo. We anticipate the detection of a 65% relative risk reduction of POUR in the experimental group in comparison with the placebo group. To detect a 65% reduction of POUR in the experimental group (2.9% anticipated) in comparison with the placebo group (8.3% anticipated) and to assure a study power of 80% with a Fisher's Exact Test and a significance level of 5% and adjusting for a drop-out rate of 2% we need 634 patients in total; 317 in each group. Our target population consists of male patients ≥ 60 yrs, scheduled for elective endoscopic inguinal hernia repair. The studied sample is appropriate to the hypothesis being tested so that any results will be appropriately generalizable.

• Study Type: Interventional
• Enrollment (Anticipated): 634
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Uwe Bieri, MD; Phone Number: +4179 268 78 37; Email: uwe.bieri@gmail.com
• Study Contact Backup: Name: Juliette Slieker, MD; Phone Number: +41 (056) 486 10 20; Email: Juliette.Slieker@ksb.ch

Study Locations

• Switzerland
  • Aargau
    • Baden, Aargau, Switzerland, 5404
      • Recruiting
      • Kantonsspital Baden
      • Contact: Juliette Slieker, MD; Phone Number: +41 56 486 10 20; Email: juliette.slieker@ksb.ch
      • Contact: Uwe Bieri, MD; Phone Number: +41792687837; Email: uwe.bieri@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Males
• ≥60 years old
• Planned uni- or bilateral endoscopic total extraperitoneal inguinal hernia repair
• Surgery scheduled more than 6 days from the time of consent
• Informed Consent as documented by signature (Appendix Informed Consent Form)

Exclusion Criteria:

• Orthostatic hypotension (feeling of dizziness after getting up from a sitting or lying position)
• Severe liver disease (Child Pugh C)
• Taking strong inhibitors of CYP3A4 (ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir/ritonavir, lopinavir, or conivaptan)
• Being on alpha-blockers (alfuzosin, doxazosin, prazosin, terazosin, tamsulosin, phenoxybenzamine, or silodosin) or a combination product containing alpha-blocker (duodart)
• History of allergy or sensitivity to tamsulosin or other alpha-blockers (alfuzosin, doxazosin, prazosin, terazosin, or phenoxybenzamine)
• Long term Indwelling urinary or suprapubic catheter
• Status post cystectomy
• Inability to provide informed consent
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamsulosin Arm; p.o.	Drug: TAMSULOSIN Mepha Ret Depocaps 0.4 mg; 0.4mg/day Tamsulosin hydrochloride ("TAMSULOSIN Mepha Ret Depocaps 0.4 mg") from 5 days prior to the day of surgery, at the day of surgery and for 1 day following surgery. (5+1+1); Other Names: Verum
Placebo Comparator: Placebo Arm; p.o.	Drug: Control Intervention; One placebo capsule matching the active study drug per day from 5 days prior to the day of surgery, at the day of surgery and for 1 day following surgery. (5+1+1); Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post operative urinary retention (Need for any catheterization postoperatively)	Need for any catheterization postoperatively (Yes/No)	up to 3 days after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first voiding after surgery	secondary outcomes in Non-POUR Patients	up to 3 days after surgery
Urinary Volume measurement at defined points in time (n)	secondary outcomes in all Patients	up to 12 hours after surgery
Volume of first micturition after surgery	secondary outcomes in Non-POUR Patients	up to 12 hours after surgery
Post-operative Pain (Quantity of Pain / VAS-Score)	Quantity of pain is verified at arrival in the PACU and at every 6 hours by the nursing staff, using the standardised numeric rating scale. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain. It is for adults and children 10 years old or older.	up to 3 days after surgery
Need for opioid analgesics post operatively	secondary outcomes in all Patients	up to 3 days after surgery
Quantity of post-operative opioid use (opioid dosage will be converted to oral morphine equivalence dose)	opioid use is documented in the patient's record, opioid dosage will be converted to oral morphine equivalence dose	up to 3 days after surgery
Intraoperative applications of opioid analgesics (Yes/No)	Opioid use during surgery is documented in the patient's record, this is a binary endpoint opioid use; (yes/ no)	intra-operative period
Quantity of intra-operative opioid use opioid dosage will be converted to oral morphine equivalence dose)	Opioid use during surgery is documented in the patient's record, opioid dosage will be converted to oral morphine equivalence dose	intra-operative period
Amount of intraoperative fluid administration	Intraoperative fluid administration (in milliliter) is documented in the patient's record	intra-operative period
International Prostate Symptom Score (IPSS score) pre-surgery (-5d)	0-7 Mildly symptomatic / 8-19 Moderately symptomatic / 20-35 Severely symptomatic	min. 5 days prior to surgery
International Prostate Symptom Score (IPSS score) post-surgery (3d)	0-7 Mildly symptomatic / 8-19 Moderately symptomatic / 20-35 Severely symptomatic	3 days post surgery
Change in International Prostate Symptom Score (IPSS score) from baseline prior to surgery (-5d) to day 3(+3d) after surgery	0-7 Mildly symptomatic / 8-19 Moderately symptomatic / 20-35 Severely symptomatic	3 days post surgery
Side-effects of study medication (orthostatic hypotension, retrograde ejaculation, Floppy-Iris-Syndrom)	Will be documented in the patient record by the study personnel, binary endpoint (Yes/No)	5 days prior to surgery (-5d) to day 3(+3d) after surgery
In hospital complications (using the evaluated standard classification for complication in surgery (Classification Grade I-V) )	secondary outcomes in all Patients	as long as the patient is labeled inpatient, on average 1-3 days
Length of hospital stay in days (Inpatients)	secondary outcomes in all Patients	as long as the patient is labeled inpatient, on average 1-3 days
Time to discharge after surgery in hours (outpatients)	secondary outcomes in all Patients	up to 12 hours after surgery
Residual urinary volume after catherization	secondary outcomes in POUR Patients	up to 12 hours after surgery
Macrohematuria	secondary outcomes in POUR Patients	3 days post surgery
Relevant injury to the urethra (Presence of a Via falsa diagnosed by a urologist)	secondary outcomes in POUR Patients	3 days post surgery
Catheter-related infections	secondary outcomes in POUR Patients	3 days post surgery
Catheter-related bladder discomfort ( (Ggrading according to the 3three Ggrades (mild, moderate, severe)	secondary outcomes in POUR Patients	3 days post surgery
Prostatitis	secondary outcomes in POUR Patients	3 days post surgery
Failed first trial without catheter (TWOC: need for a second catheter insertion due to insufficient voiding after TWOC).	secondary outcomes in POUR Patients	1 day post surgery

Collaborators and Investigators

• Sponsor: Antonio Nocito, MD
• Investigators: Principal Investigator: Antonio Nocito, Prof, Kantonsspital Baden AG, Im Ergel 1, 5404 Baden, Switzerland

Publications and helpful links

General Publications

• Bieri U, Slieker J, Hefermehl LJ, Soppe S, Teufelberger G, Tedaldi R, Graf N, Bieri M, Nocito A. Randomised, quadruple blinded, placebo controlled, multicentre trial investigating prophylactic tamsulosin in prevention of postoperative urinary retention in men after endoscopic total extraperitoneal inguinal hernia repair (STOP-POUR trial): a study protocol. BMJ Open. 2021 Dec 7;11(12):e048911. doi: 10.1136/bmjopen-2021-048911.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2020
• Primary Completion (Anticipated): December 30, 2024
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: July 27, 2020
• First Posted (Actual): July 29, 2020

Study Record Updates

• Last Update Posted (Estimate): March 10, 2023
• Last Update Submitted That Met QC Criteria: March 9, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: IPSS; Urinary Retention; Inguinal Hernia Repair; alpha-1 adrenergic receptor antagonists
• Additional Relevant MeSH Terms: Urologic Diseases; Urination Disorders; Pathological Conditions, Anatomical; Hernia, Abdominal; Hernia; Hernia, Inguinal; Urinary Retention; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Urological Agents; Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Tamsulosin
• Other Study ID Numbers: 2020-00569

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified participant data are available upon reasonable request from https://orcid.org/0000-0002-7339-1458.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No