Evaluation of Naloxegol in the Prevention of POI After Cystectomy

NCT ID: NCT04219046

Last Updated: 2020-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 102 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-31
• Study Completion Date: 2022-12-31

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.

Conditions

Bladder Cancer; Cystostomy; Complications

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Experimental Treatment

ERAS program with administration of experimental treatment: Naloxegol 25mg administrated once daily from surgery for up to 7 days

Group Type: EXPERIMENTAL

Naloxégol oxalate

Intervention Type: DRUG

Oral administration once daily

Placebo

ERAS program with administration of placebo: Placebo administrated once daily from surgery for up to 7 days

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

Oral administration once daily

Interventions

Naloxégol oxalate

Oral administration once daily

Intervention Type: DRUG

Placebo oral tablet

Oral administration once daily

Intervention Type: DRUG

Other Intervention Names

Naloxegol; Placebo

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Paoli-Calmettes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Géraldine Pignot, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Isntitut Paoli-Calmettes

Central Contacts

Dominique GENRE, MD

Role: CONTACT

drci.up@ipc.unicancer.fr

33 4 91 22 37 78

Carine Cormary-Feuillet, PhD

Role: CONTACT

drci.up@ipc.unicancer.fr

33 4 91 22 58 82

Other Identifiers

ANTAGOCYST-01-IPC 2019-034

Identifier Type: -

Identifier Source: org_study_id