Evaluation of Naloxegol in the Prevention of POI After Cystectomy

Study Overview
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Brief Summary
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Postoperative ileus (POI) is defined as a transient reduction of bowel motility that prevents effective transit of bowel content and tolerance of oral intake following surgical interventions, especially after radical cystectomy. It remains a major factor associated with postoperative morbidity, length of hospital stay and medical costs. In order to optimize perioperative care for patients undergoing radical cystectomy in a context of an ERAS (Enhanced Recovery After Surgery) program, we will evaluate the effectiveness of systemic pharmacologic opioid antagonist treatment.

Detailed Description
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Radical cystectomy (RC) with urinary diversion represents the gold standard treatment for muscle-invasive bladder cancer. Postoperative ileus (POI) is defined as a transient reduction of bowel motility that prevents effective transit of bowel content and tolerance of oral intake following surgical interventions, especially after RC. It remains a major factor associated with postoperative morbidity, length of hospital stay and medical costs. Faster gastrointestinal recovery and prevention of POI are at the heart of ERAS (Enhanced Recovery After Surgery) protocols. In order to optimize the post-operative consequences of patients operated on for a cystectomy within the framework of a RAAC program, several provisions aim to alleviate post-operative gastrointestinal dysfunctions. Naloxegol, peripherally acting µ-opioid receptor antagonist, is currently approved for opioid-induced constipation in Chronic Non-Cancer Pain, but its potential interest to prevent POI has never been assessed. In this randomized, double-blind, placebo-controlled trial, the administration of Naloxegol for a limited duration as part of ERAS (Enhanced Recovery After Surgery) program will be evaluated to reduce the time of hospital discharge (length of stay) and to reduce the rate of postoperative complications. Priamry and secondary objectives will be compared between naloxegol and placebo groups.

Official Title
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Evaluation of Naloxegol, a Peripherally Acting µ-opioid Receptor Antagonist, in the Prevention of Postoperative Ileus After Cystectomy

Conditions
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Bladder Cancer, Cystostomy; Complications

Intervention / Treatment
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* Drug: Naloxégol oxalate
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 18 years Informed consent signed Histopathological confirmation of bladder cancer Patients undergoing radical cystectomy and urinary diversion for an oncological indication Patients able to understand the study procedures, agreed to participate in the study program Patients affiliated to the national Social Security regimen or beneficiary of this regimen Exclusion Criteria: Unwilling to undergo cystectomy Cystectomy for non-oncological indication Patients with concomitant upper urinary tract disease Previous total colectomy, gastrectomy, or gastric bypass, or functional colostomy or ileostomy Previous pelvic radiotherapy for prostate or bladder cancer Patients having taken opioids for more than seven days before surgery (to prevent peripheral withdrawal effects) Patients treated with drugs metabolized by certain enzymes (CYP3A4 and P-gp) Patients with severe hepatic impairment Patients with end-stage renal disease Patients with heart failure Patients with severe dementia that impacts daily functioning Pregnant and lactating females Not postmenopausal females and of childbearing potential and not using an accepted method of birth control (i.e, surgical sterilization; intrauterine contraceptive device; oral contraceptive, diaphragm) Patients participated in another investigational drug or medical device study within 30 days of surgery or planning to be enrolled in another investigational drug or medical device study or any study in which active patient participation was required outside normal hospital data collection during the course of this study Patients deprived of liberty or placed under the authority of a tutor or curator

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Double-blind, placebo-controlled
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Treatment<br>ERAS program with administration of experimental treatment: Naloxegol 25mg administrated once daily from surgery for up to 7 days | Drug: Naloxégol oxalate<br>* Oral administration once daily<br>* Other names: Naloxegol;|
| Placebo Comparator: Placebo<br>ERAS program with administration of placebo: Placebo administrated once daily from surgery for up to 7 days | Drug: Placebo oral tablet<br>* Oral administration once daily<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of hospital discharge | Comparaison between treatment group and placebo group for post-operative length of stay between the date of hospital discharge and the date of surgery | Date at which treatment is initiated and date of hospital discharge (up to 12 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of reinsertion of nasogastric tube | Comparaison between treatment group and placebo group for rate of reinsertion of nasogastric tube | From post-surgery to hospital discharge (up to 12 days) | 
| Time to reach gastrointestinal recovery | Comparaison between treatment group and placebo group for time ot reach gastrointestinal recovery | Date at which the patient has the first gaz from post-surgery (up to 12 days) | 
| Rate of 30-day postoperative complications | Comparaison between treatment group and placebo group for rate of 30-day postoperative complications with Clavien-Dindo classification grade I-V | Postoperative complications from surgery, to 30-day postsurgery and to 90 postsurgery with Clavien-Dindo classification (up to 3 motnhs) | 
| Rate of major postoperative complications of 90-day postoperative period | Comparaison between treatment group and placebo group for rate of major postoperative complications with Clavien-Dindo classification grade III-IV-V | Major postoperative complications from surgery to 90 postsurgery with Clavien-Dindo classification (up to 3 motnhs) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radical cystectomy, Postoperative ileus, Enhanced Recovery After Surgery