Study to Prevent Postoperative Urinary Retention

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Inguinal Hernia, Urinary Retention

Intervention / Treatment
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* Drug: TAMSULOSIN Mepha Ret Depocaps 0.4 mg
* Drug: Control Intervention


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tamsulosin Arm<br>p.o. | Drug: TAMSULOSIN Mepha Ret Depocaps 0.4 mg<br>* 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)<br>* Other names: Verum;|
| Placebo Comparator: Placebo Arm<br>p.o. | Drug: Control Intervention<br>* 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)<br>* Other names: Placebo;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Urinary Retention, Inguinal Hernia Repair, alpha-1 adrenergic receptor antagonists, IPSS