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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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.

Brief Summary:

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

Detailed Summary:
Sponsor: Cubist Pharmaceuticals LLC

Current Primary Outcome: 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 ]

Original Primary Outcome: Time to achieve recovery of both upper and lower GI function as measured by a composite endpoint of time to the first bowel movement and time to tolerate first solid food. This endpoint is referred to as GI2. [ Time Frame: up to 10 days ]

Current Secondary Outcome:

• 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 ]

  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 ]

  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

Original Secondary Outcome:

• Time to ready for discharge [ Time Frame: Up to 10 days ]
• Time to discharge order written [ Time Frame: Up to 10 days ]
• Length of hospital stay [ Time Frame: Until hospital discharge ]
• incidence of adverse events [ Time Frame: up to 30 days or until resolution ]

Dates:
Date Received: June 27, 2008
Date Started: March 2009
Date Completion:
Last Updated: January 6, 2016
Last Verified: January 2016