A Study of Alvimopan for the Management of Postoperative Ileus in Participants Undergoing Radical Cystectomy

A Phase 4, Multicenter, Double-Blind, Placebo-Controlled, Parallel Study of Alvimopan for the Management of Postoperative Ileus in Subjects Undergoing Radical Cystectomy.

This study is being conducted to determine whether alvimopan can accelerate recovery of gastrointestinal function following radical cystectomy when compared with a placebo. Secondary objectives of the study are:

• to evaluate the effect of alvimopan on hospital length of stay
• to evaluate the effect of alvimopan on prespecified postoperative ileus (POI)-related morbidities
• to evaluate the overall and cardiovascular safety of alvimopan

Study Overview

• Status: Completed
• Conditions: Postoperative Ileus
• Intervention / Treatment: Drug: Placebo; Drug: Alvimopan

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Laguna Hills, California, United States, 92653
      • Saddleback Memorial Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medical Center
    • Chicago, Illinois, United States, 60637
      • University of Chicago, Section of Urology MC6038
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Hospital
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • CRC of Jackson
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Hospitals
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Bend, Oregon, United States, 97701
      • Bend Memorial Clinic
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University Knight Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center, Department of Urology Surgery
  • Texas
    • Houston, Texas, United States, 77030
      • The Methodist Hospital
    • Houston, Texas, United States, 77030
      • The University of Texas Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• are either Male or Female at least 18 years of age
• are scheduled for radical cystectomy
• are scheduled to receive postoperative pain management with intravenous participant-controlled opioid analgesics

Exclusion Criteria:

• are scheduled for a partial cystectomy
• have taken more than 3 doses of opioids (oral or parenteral) within 7 days before the day of surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Alvimopan; 12 milligrams (mg) Alvimopan, 12mg, capsule. Administered orally. One 30 minutes to 5 hours before the scheduled start of surgery on Day 0, and twice daily beginning on Postoperative Day 1 (POD 1) until hospital discharge or for a maximum of 7 days (up to 15 doses) of postoperative treatment	Drug: Alvimopan; Other Names: Entereg; ADL2698
PLACEBO_COMPARATOR: Placebo; 300 mg polyethylene glycol in a capsule Administered orally at least 30 minutes and no later than 5 hours before the scheduled start of surgery on Day 0. On Day 1, a single dose of placebo was given twice a day for a maximum of 7 days in hospital after surgery.	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Time to Achieve GI2 Analyzed by Kaplan-Meier (KM) Estimates and Cox Proportional Hazards (PH) Model	Time to achieve recovery of gastrointestinal (GI) function as measured by a composite endpoint of both upper GI recovery (toleration of solid food) and lower GI recovery (first bowel movement [BM]) using KM Estimates and Cox PH Model. This endpoint was referred to as GI2. GI2 was calculated as GI2 = maximum (max) (solids, BM). The KM estimate reported below is biased because of the censoring of the last observation. Censoring Rules for Study Participants who: Completed: the censored time for the event was determined as: censored time = minimum [maximum (time of/to last GI assessment, time of/to hospital discharge order written), study duration]. Discontinued: censored time = maximum (time of/to last GI assessment, time of/to discontinuation)	From day of surgery (Day 0) up to 10 days in hospital

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Time to Ready for Discharge From Hospital Analyzed by KM Estimates and Cox PH Model	The endpoint of "time to ready for discharge" was based solely on the recovery of GI function as determined by the surgeon. The KM estimate reported below is biased because of the censoring of the last observation. Censoring Rules for Study Participants who: Completed: the censored time for the event was determined as: censored time = minimum [maximum (time of/to last GI assessment, time of/to hospital discharge order written), study duration]. Discontinued: censored time = maximum (time of/to last GI assessment, time of/to discontinuation)	Day of surgery (Day 0) up to 10 days in hospital
Mean Time to Discharge Order Written (DOW) Using KM Estimates	The KM estimate reported below is biased because of the censoring of the last observation. Censoring Rules for Study Participants who: Completed: the censored time for the event was determined as: censored time = minimum [maximum (time of/to last GI assessment, time of/to hospital discharge order written), study duration]. Discontinued: censored time = maximum (time of/to last GI assessment, time of/to discontinuation)	Day of surgery (Day 0) up to 10 days in hospital
Postoperative Length of Stay (LOS)	The postoperative LOS was determined by the difference between the date of hospital DOW and the date of surgery; that is, the postoperative LOS for a participant was calculated as follows: (date of DOW) - (date of surgery).	Day of surgery (Day 0) to the day of hospital DOW
Percentage of Participants Considered Postoperative LOS Responders	A participant was considered a postoperative LOS responder if the postoperative LOS was less than or equal to 7 days. The postoperative LOS for a participant was calculated as follows: (date of DOW) - (date of surgery). Participants with missing data were considered nonresponders.	Day of surgery (Day 0) up to 7 days after surgery
Percentage of Participants With Postoperative Morbidity (POM)	POM was defined as the need for postoperative nasogastric (NG) tube insertion, hospital stay prolonged because of postoperative ileus (POI) (as determined by the investigator), or readmission (readmiss) to the hospital (hosp) for POI within 7 days (d) after discharge.	During hospitalization or within 7 days after discharge
Percentage of Participants Considered G12 Responders at 5 Cutoff Time Points	Time to achieve recovery of GI function was measured by a composite endpoint of time to first BM and time to tolerate first solid food (solids). This endpoint was referred to as GI2, and GI2 was calculated as follows: GI2 = max (solids, BM). GI2 responders were defined as those participants who met all the following criteria: achieved GI2 by the cutoff point, did not have hospital stay prolonged because of POI, and did not have readmission for POI within 7 days of actual hospital discharge. Postsurgery Days (PSD) were measured in 24 hour increments after surgery.	Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7
Percentage of Participants Considered DOW Responders at 5 Cutoff Time Points	DOW responders were defined as those participants who met all the following criteria: achieved DOW by the cutoff point, did not have hospital stay prolonged because of POI, and did not have readmission for POI within 7 days of actual hospital discharge. PSD were measured in 24 hour increments after surgery.	Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7
Percentage of Participants With Blinded Adjudicated Cardiovascular (CV) Events	CV events of interest included congestive heart failure, CV death, cerebrovascular accident, myocardial infarction, serious arrhythmia, and unstable angina. CV events were adjudicated by a blinded external committee.	Baseline to 30 days post discharge

Collaborators and Investigators

• Sponsor: Cubist Pharmaceuticals LLC
• Investigators: Study Director: Lee Techner, DPM, Cubist Pharmaceuticals LLC

Publications and helpful links

General Publications

• Lee CT, Chang SS, Kamat AM, Amiel G, Beard TL, Fergany A, Karnes RJ, Kurz A, Menon V, Sexton WJ, Slaton JW, Svatek RS, Wilson SS, Techner L, Bihrle R, Steinberg GD, Koch M. Alvimopan accelerates gastrointestinal recovery after radical cystectomy: a multicenter randomized placebo-controlled trial. Eur Urol. 2014 Aug;66(2):265-72. doi: 10.1016/j.eururo.2014.02.036. Epub 2014 Feb 26.

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (ACTUAL): January 1, 2012
• Study Completion (ACTUAL): January 1, 2012

Study Registration Dates

• First Submitted: June 27, 2008
• First Submitted That Met QC Criteria: June 27, 2008
• First Posted (ESTIMATE): July 2, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 8, 2016
• Last Update Submitted That Met QC Criteria: January 6, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Keywords: ileus; POI
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Obstruction; Ileus; Gastrointestinal Agents; Alvimopan
• Other Study ID Numbers: 3753-002; 14CL403 (OTHER: Cubist Study Number)