Evaluation of Naloxegol in the Prevention of POI After Cystectomy (ANTAGOCYST)
Primary Purpose
Bladder Cancer, Cystostomy; Complications
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Naloxégol oxalate
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for Bladder Cancer focused on measuring Radical cystectomy, Postoperative ileus, Enhanced Recovery After Surgery
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Experimental Treatment
Placebo
Arm Description
ERAS program with administration of experimental treatment: Naloxegol 25mg administrated once daily from surgery for up to 7 days
ERAS program with administration of placebo: Placebo administrated once daily from surgery for up to 7 days
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Rate of reinsertion of nasogastric tube
Comparaison between treatment group and placebo group for rate of reinsertion of nasogastric tube
Time to reach gastrointestinal recovery
Comparaison between treatment group and placebo group for time ot reach gastrointestinal recovery
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
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
Full Information
NCT ID
NCT04219046
First Posted
December 20, 2019
Last Updated
July 27, 2020
Sponsor
Institut Paoli-Calmettes
1. Study Identification
Unique Protocol Identification Number
NCT04219046
Brief Title
Evaluation of Naloxegol in the Prevention of POI After Cystectomy
Acronym
ANTAGOCYST
Official Title
Evaluation of Naloxegol, a Peripherally Acting µ-opioid Receptor Antagonist, in the Prevention of Postoperative Ileus After Cystectomy
Study Type
Interventional
2. Study Status
Record Verification Date
January 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 2021 (Anticipated)
Primary Completion Date
September 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Paoli-Calmettes
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bladder Cancer, Cystostomy; Complications
Keywords
Radical cystectomy, Postoperative ileus, Enhanced Recovery After Surgery
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Randomized, Double-blind, placebo-controlled
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
102 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Experimental Treatment
Arm Type
Experimental
Arm Description
ERAS program with administration of experimental treatment: Naloxegol 25mg administrated once daily from surgery for up to 7 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
ERAS program with administration of placebo: Placebo administrated once daily from surgery for up to 7 days
Intervention Type
Drug
Intervention Name(s)
Naloxégol oxalate
Other Intervention Name(s)
Naloxegol
Intervention Description
Oral administration once daily
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Other Intervention Name(s)
Placebo
Intervention Description
Oral administration once daily
Primary Outcome Measure Information:
Title
Time of hospital discharge
Description
Comparaison between treatment group and placebo group for post-operative length of stay between the date of hospital discharge and the date of surgery
Time Frame
Date at which treatment is initiated and date of hospital discharge (up to 12 days)
Secondary Outcome Measure Information:
Title
Rate of reinsertion of nasogastric tube
Description
Comparaison between treatment group and placebo group for rate of reinsertion of nasogastric tube
Time Frame
From post-surgery to hospital discharge (up to 12 days)
Title
Time to reach gastrointestinal recovery
Description
Comparaison between treatment group and placebo group for time ot reach gastrointestinal recovery
Time Frame
Date at which the patient has the first gaz from post-surgery (up to 12 days)
Title
Rate of 30-day postoperative complications
Description
Comparaison between treatment group and placebo group for rate of 30-day postoperative complications with Clavien-Dindo classification grade I-V
Time Frame
Postoperative complications from surgery, to 30-day postsurgery and to 90 postsurgery with Clavien-Dindo classification (up to 3 motnhs)
Title
Rate of major postoperative complications of 90-day postoperative period
Description
Comparaison between treatment group and placebo group for rate of major postoperative complications with Clavien-Dindo classification grade III-IV-V
Time Frame
Major postoperative complications from surgery to 90 postsurgery with Clavien-Dindo classification (up to 3 motnhs)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Dominique GENRE, MD
Phone
33 4 91 22 37 78
Email
drci.up@ipc.unicancer.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Carine Cormary-Feuillet, PhD
Phone
33 4 91 22 58 82
Email
drci.up@ipc.unicancer.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Géraldine Pignot, MD, PhD
Organizational Affiliation
Isntitut Paoli-Calmettes
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Evaluation of Naloxegol in the Prevention of POI After Cystectomy
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