Alvimopan Versus Placebo in Patients Undergoing Radical Cystectomy on an Enhanced Recovery Protocol

A Randomized, Double-blind, Single-Center Trial of Alvimopan (Entereg) Versus Placebo in Patients Undergoing Radical Cystectomy and Urinary Diversion on an Enhanced Recovery After Surgery ERAS Protocol

To determine if Alvimopan during open or robotic radical cystectomy with urinary diversion results in quicker return of bowel function (GI-2 recovery = time to upper [first toleration of solid food] and lower [first bowel movement] gastrointestinal recovery) compared to placebo.

Study Overview

• Status: Recruiting
• Conditions: Bladder Cancer
• Intervention / Treatment: Drug: Alvimopan; Drug: Placebo

Detailed Description

A prospective, randomized, single-center double blind trial of Alvimopan versus placebo for improving patient outcomes and cost during radical cystectomy and urinary diversion will be performed. A randomized trial is necessary to control for all the known and unknown confounders associated with instituting this novel intervention into a surgical procedure. We will recruit 136 subjects (63 patients in each arm of the study per sample size calculation below, plus additional 10 subjects to account for drop outs). A control group will be administered a placebo in order to directly compare if the Alvimopan intervention is effective.

• Study Type: Interventional
• Enrollment (Estimated): 136
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Martin Barylak; Phone Number: 6175258274; Email: mbarylak@bwh.harvard.edu
• Study Contact Backup: Name: Anjali Vasavada; Phone Number: 6175258274; Email: AVASAVADA@BWH.HARVARD.EDU

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Martin Barylak; Phone Number: 617-525-8274; Email: mbarylak@bwh.harvard.edu
      • Principal Investigator: Mark A Preston, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing radical cystectomy and urinary diversion via open or robotic approach.
• Man or woman between the ages of 18 and 85.
• American Society of Anesthesiologists (ASA) Physical Status Score of class 1-4
• Ileal conduit or ileal neobladder urinary diversion
• Able to understand the study procedures, agreed to participate in the study program, and voluntarily provided informed consent

Exclusion criteria:

• Patients who met any of the following criteria were excluded from participating in the study:
• Scheduled for a partial cystectomy
• Previous total colectomy, gastrectomy, or gastric bypass, or functional colostomy or ileostomy
• More than three doses of opioids (oral or parenteral) within 7 days before the day of surgery
• Chemotherapy for bladder cancer within 1 month of scheduled surgery; prior neoadjuvant chemotherapy allowed.
• Pregnant (identified by a positive serum pregnancy test administered after the initial screening process and before the commencement of study activities) or lactating, or not postmenopausal (no menses for at least 1 year) and of childbearing potential and not using an accepted method of birth control (i.e, surgical sterilization; intrauterine contraceptive device; oral contraceptive, diaphragm, or condom in combination with contraceptive cream, jelly, or foam; or abstinence) (Participants will be asked to use birth control for the entire study and for at least 2 weeks after the last dose of study drug.)
• 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
• Clinically significant laboratory abnormalities at screening that would have resulted in the cancellation of surgery
• Using illicit drugs or abusing alcohol
• History of previous surgeries, illness, or behavior (eg, depression, psychosis) that in the opinion of the investigator might have confounded the study results or might have posed additional risk in administering the study procedures
• Patients with severe dementia (as determined from medical records and history. Severe dementia will be defined as dementia that impacts daily functioning.)
• Patients with severe hepatic impairment.
• Patients with end-stage renal disease.
• Patients with heart failure. .
• Patients with complete gastrointestinal obstruction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral Alvimopan; Oral Alvimopan (Entereg, Merck) 12 mg between 30 minutes and 3 hours before surgery start and twice-daily oral doses postoperatively beginning on day one (AM and PM dosing) until hospital discharge or a maximum of 7 days (15 in-hospital doses).	Drug: Alvimopan; To determine if Alvimopan during radical cystectomy with urinary diversion results in faster return of bowel function.; Other Names: Entereg
Placebo Comparator: Matching Placebo; Matching placebo between 30 minutes and 3 hours before surgery start and twice-daily oral doses postoperatively beginning on day one (AM and PM dosing) until hospital discharge or a maximum of 7 days (15 in-hospital doses).	Drug: Placebo; To determine if placebo during radical cystectomy with urinary diversion results in faster return of bowel function.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Return of Bowel Function	To achieve quicker time to return bowel function measured by a composite endpoint of both upper GI recovery (GI-2 recovery = [first toleration of solid food] and lower (first bowel movement) gastrointestinal recovery, taking Alvimopan during radical cystectomy, compared to placebo.	From Day of surgery (Day 0) to Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Post-operative Length of Stay	Post operative LOS was determined by the difference between the date of hospital discharge and the date of surgery; that is the postoperative LOS for a participant was calculated as follows:(date of discharge)-(date of surgery).	Day of surgery (Day 0) to Day of Discharge (Up to Day 30)
Post-operative Morbidity	POM defined as need for nasogastric (NG) tube insertion, hospital stay prolonged because of post-operative ileus (POI) beyond 10 days, or readmission to hospital for POI within 7 days after discharge.	During hospitalization up to 7 days after surgery
30 Day Complications	Any Clavien Grade II-V complication.	Day of surgery (Day 0) to Day 30
Readmission to Hospital	Any readmission to hospital for > 24 hours after discharge.	Day of Discharge (Up to Day 30)
Open vs Robotic Radical Cystectomy	To determine if Alvimopan during open or robotic radical cystectomy with urinary diversion results in decreased time to GI2 recovery	Day of Surgery (Day 0)
Cost Analysis	To evaluate costs of surgery and post-operative care between alvimopan and placebo in patients having a radical cystectomy and urinary diversion.	Day of surgery (Day 0) to Day 30

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Mark A Preston, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Vora AA, Harbin A, Rayson R, Christiansen K, Ghasemian R, Hwang J, Verghese M. Alvimopan provides rapid gastrointestinal recovery without nasogastric tube decompression after radical cystectomy and urinary diversion. Can J Urol. 2012 Jun;19(3):6293-8.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Estimated): December 1, 2023
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: March 13, 2017
• First Submitted That Met QC Criteria: July 11, 2017
• First Posted (Actual): July 13, 2017

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Gastrointestinal Agents; Alvimopan
• Other Study ID Numbers: 2017P000330

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No