Clinical trial NCT04219046: Evaluation of Naloxegol in the Prevention of POI After Cystectomy
Official title: Evaluation of Naloxegol, a Peripherally Acting µ-opioid Receptor Antagonist, in the Prevention of Postoperative Ileus After Cystectomy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Bladder Cancer
Cystostomy; Complications
Keywords: Radical cystectomy
Postoperative ileus
Enhanced Recovery After Surgery
Lead sponsor: Institut Paoli-Calmettes
Sponsor class: OTHER
First posted: 2020-01-06
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, Double-blind, placebo-controlled
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Time of hospital discharge
timeFrame: Date at which treatment is initiated and date of hospital discharge (up to 12 days)
Secondary outcomes:
measure: Rate of reinsertion of nasogastric tube
timeFrame: From post-surgery to hospital discharge (up to 12 days)
measure: Time to reach gastrointestinal recovery
timeFrame: Date at which the patient has the first gaz from post-surgery (up to 12 days)
measure: Rate of 30-day postoperative complications
timeFrame: Postoperative complications from surgery, to 30-day postsurgery and to 90 postsurgery with Clavien-Dindo classification (up to 3 motnhs)
measure: Rate of major postoperative complications of 90-day postoperative period
timeFrame: Major postoperative complications from surgery to 90 postsurgery with Clavien-Dindo classification (up to 3 motnhs)
Other outcomes:
Locations:
Study officials:
affiliation: Isntitut Paoli-Calmettes
name: Géraldine Pignot, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: