search
Back to results

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

Primary Purpose

Postoperative Ileus

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Alvimopan
Placebo
Sponsored by
Cubist Pharmaceuticals LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Postoperative Ileus focused on measuring ileus, POI

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Saddleback Memorial Medical Center
  • University of Colorado Hospital
  • University of Miami
  • H. Lee Moffitt Cancer Center & Research Institute
  • The University of Chicago Medical Center
  • University of Chicago, Section of Urology MC6038
  • Indiana University Hospital
  • Ochsner Clinic Foundation
  • University of Michigan Health System
  • University of Minnesota Hospital
  • Mayo Clinic
  • CRC of Jackson
  • University of North Carolina Hospitals
  • Wake Forest University Baptist Medical Center
  • Cleveland Clinic
  • Bend Memorial Clinic
  • Oregon Health and Science University Knight Cancer Institute
  • Vanderbilt University Medical Center, Department of Urology Surgery
  • The Methodist Hospital
  • The University of Texas MD Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Alvimopan

Placebo

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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)
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)
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).
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.
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.
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.
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.
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.

Full Information

First Posted
June 27, 2008
Last Updated
January 6, 2016
Sponsor
Cubist Pharmaceuticals LLC
search

1. Study Identification

Unique Protocol Identification Number
NCT00708201
Brief Title
A Study of Alvimopan for the Management of Postoperative Ileus in Participants Undergoing Radical Cystectomy
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.
Study Type
Interventional

2. Study Status

Record Verification Date
January 2016
Overall Recruitment Status
Completed
Study Start Date
March 2009 (undefined)
Primary Completion Date
January 2012 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cubist Pharmaceuticals LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Postoperative Ileus
Keywords
ileus, POI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
280 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Alvimopan
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Alvimopan
Other Intervention Name(s)
ADL2698, Entereg
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Mean Time to Achieve GI2 Analyzed by Kaplan-Meier (KM) Estimates and Cox Proportional Hazards (PH) Model
Description
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 Frame
From day of surgery (Day 0) up to 10 days in hospital
Secondary Outcome Measure Information:
Title
Mean Time to Ready for Discharge From Hospital Analyzed by KM Estimates and Cox PH Model
Description
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)
Time Frame
Day of surgery (Day 0) up to 10 days in hospital
Title
Mean Time to Discharge Order Written (DOW) Using KM Estimates
Description
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 Frame
Day of surgery (Day 0) up to 10 days in hospital
Title
Postoperative Length of Stay (LOS)
Description
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).
Time Frame
Day of surgery (Day 0) to the day of hospital DOW
Title
Percentage of Participants Considered Postoperative LOS Responders
Description
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.
Time Frame
Day of surgery (Day 0) up to 7 days after surgery
Title
Percentage of Participants With Postoperative Morbidity (POM)
Description
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.
Time Frame
During hospitalization or within 7 days after discharge
Title
Percentage of Participants Considered G12 Responders at 5 Cutoff Time Points
Description
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.
Time Frame
Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7
Title
Percentage of Participants Considered DOW Responders at 5 Cutoff Time Points
Description
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.
Time Frame
Day of surgery (Day 0) through PSD 3, PSD 4, PSD 5, PSD 6, and PSD 7
Title
Percentage of Participants With Blinded Adjudicated Cardiovascular (CV) Events
Description
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 Frame
Baseline to 30 days post discharge

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lee Techner, DPM
Organizational Affiliation
Cubist Pharmaceuticals LLC
Official's Role
Study Director
Facility Information:
Facility Name
Saddleback Memorial Medical Center
City
Laguna Hills
State/Province
California
ZIP/Postal Code
92653
Country
United States
Facility Name
University of Colorado Hospital
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
The University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Chicago, Section of Urology MC6038
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University Hospital
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Ochsner Clinic Foundation
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
University of Minnesota Hospital
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
CRC of Jackson
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39202
Country
United States
Facility Name
University of North Carolina Hospitals
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Wake Forest University Baptist Medical Center
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Bend Memorial Clinic
City
Bend
State/Province
Oregon
ZIP/Postal Code
97701
Country
United States
Facility Name
Oregon Health and Science University Knight Cancer Institute
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Vanderbilt University Medical Center, Department of Urology Surgery
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
The Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24630419
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs