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 ( Cubist Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00708201
First received: June 27, 2008
Last updated: June 4, 2015
Last verified: June 2015

June 27, 2008
June 4, 2015
March 2009
January 2012   (final data collection date for primary outcome measure)
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)

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 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00708201 on ClinicalTrials.gov Archive Site
  • 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.
  • Time to ready for discharge [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
  • Time to discharge order written [ Time Frame: Up to 10 days ] [ Designated as safety issue: No ]
  • Length of hospital stay [ Time Frame: Until hospital discharge ] [ Designated as safety issue: No ]
  • incidence of adverse events [ Time Frame: up to 30 days or until resolution ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
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
Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Postoperative Ileus
  • Drug: Alvimopan
    Other Names:
    • ADL2698
    • Entereg
  • Drug: Placebo
  • 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

    Intervention: Drug: Alvimopan
  • 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.

    Intervention: Drug: Placebo
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
280
January 2012
January 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00708201
14CL403
Yes
Cubist Pharmaceuticals Holdings LLC ( Cubist Pharmaceuticals )
Cubist Pharmaceuticals
Not Provided
Study Director: Lee Techner, DPM Cubist Pharmaceuticals Holdings LLC
Cubist Pharmaceuticals Holdings LLC
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP