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

Study Overview
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Brief Summary
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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

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

Conditions
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Postoperative Ileus

Intervention / Treatment
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* Drug: Alvimopan
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alvimopan<br>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<br> <br> * Other names: Entereg;|
| Placebo Comparator: Placebo<br>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<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ileus, POI