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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Cubist Pharmaceuticals Holdings LLC
ClinicalTrials.gov Identifier:
NCT00708201
First received: June 27, 2008
Last updated: June 4, 2015
Last verified: June 2015
  Purpose

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

Condition Intervention Phase
Postoperative Ileus
Drug: Alvimopan
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 4, Multicenter, Double-Blind, Placebo-Controlled, Parallel Study of Alvimopan for the Management of Postoperative Ileus in Subjects Undergoing Radical Cystectomy.

Resource links provided by NLM:


Further study details as provided by Cubist Pharmaceuticals Holdings LLC:

Primary Outcome Measures:
  • Mean Time to Achieve GI2 Analyzed by Kaplan-Meier (KM) Estimates and Cox Proportional Hazards (PH) Model [ Time Frame: From day of surgery (Day 0) up to 10 days in hospital ] [ Designated as safety issue: No ]

    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)



Secondary Outcome Measures:
  • Mean Time to Ready for Discharge From Hospital Analyzed by KM Estimates and Cox PH Model [ Time Frame: Day of surgery (Day 0) up to 10 days in hospital ] [ Designated as safety issue: No ]

    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)


  • Mean Time to Discharge Order Written (DOW) Using KM Estimates [ Time Frame: Day of surgery (Day 0) up to 10 days in hospital ] [ Designated as safety issue: No ]

    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)


  • Postoperative Length of Stay (LOS) [ Time Frame: Day of surgery (Day 0) to the day of hospital DOW ] [ Designated as safety issue: No ]
    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).

  • Percentage of Participants Considered Postoperative LOS Responders [ Time Frame: Day of surgery (Day 0) up to 7 days after surgery ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Postoperative Morbidity (POM) [ Time Frame: During hospitalization or within 7 days after discharge ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Considered G12 Responders at 5 Cutoff Time Points [ Time Frame: Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants Considered DOW Responders at 5 Cutoff Time Points [ Time Frame: Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Blinded Adjudicated Cardiovascular (CV) Events [ Time Frame: Baseline to 30 days post discharge ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 280
Study Start Date: March 2009
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • ADL2698
  • Entereg
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00708201

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

No publications provided by Cubist Pharmaceuticals Holdings LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Cubist Pharmaceuticals Holdings LLC
ClinicalTrials.gov Identifier: NCT00708201     History of Changes
Other Study ID Numbers: 14CL403
Study First Received: June 27, 2008
Results First Received: September 10, 2013
Last Updated: June 4, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Cubist Pharmaceuticals Holdings LLC:
ileus
POI

Additional relevant MeSH terms:
Ileus
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Intestinal Obstruction
Alvimopan
Gastrointestinal Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015