Postoperative IleusPhase 4NCT00708201
A Study of Alvimopan for the Management of Postoperative Ileus in Participants Undergoing Radical Cystectomy
A Phase 4 study testing Alvimopan in people with Postoperative Ileus, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 20 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Ileus
- What is being tested?
- Alvimopan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 280 participants
- Where
- 20 sitesUnited States
- Study dates
- Mar 2009to Jan 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
20 sites in 1 country.
20 sites in 1 country
United States20 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109
University of Colorado Hospital
Aurora, Colorado, 80045
Bend Memorial Clinic
Bend, Oregon, 97701
University of North Carolina Hospitals
Chapel Hill, North Carolina, 27599
The University of Chicago Medical Center
Chicago, Illinois, 60637
University of Chicago, Section of Urology MC6038
Chicago, Illinois, 60637
Cleveland Clinic
Cleveland, Ohio, 44195
The Methodist Hospital
Houston, Texas, 77030
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University Hospital
Indianapolis, Indiana, 46202
CRC of Jackson
Jackson, Mississippi, 39202
Saddleback Memorial Medical Center
Laguna Hills, California, 92653
University of Miami
Miami, Florida, 33136
University of Minnesota Hospital
Minneapolis, Minnesota, 55455
Vanderbilt University Medical Center, Department of Urology Surgery
Nashville, Tennessee, 37232
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121
Oregon Health and Science University Knight Cancer Institute
Portland, Oregon, 97239
Mayo Clinic
Rochester, Minnesota, 55905
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612
Wake Forest University Baptist Medical Center
Winston-Salem, North Carolina, 27157
About this study
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.
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
- Conditions
- Postoperative Ileus
- Being tested
- Alvimopan, Placebo
- Keywords
- ileus, POI
- Medical subject headings
- Ileus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AlvimopanDrug
Also called ADL2698, Entereg
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Alvimopan | Experimental | 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 Receives: Drug: Alvimopan |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: From day of surgery (Day 0) up to 10 days in hospital
Secondary outcomes (8)
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)
Measured: 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)
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to 30 days post discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2008 (estimated)
- Study startMar 2009
- Primary completionJan 2012
- Study completionJan 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Postoperative IleusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 280 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lee Techner, DPM, Study director, Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00708201
- Sponsor's protocol ID
- 3753-002
- Other IDs
- 14CL403
- Status last verified
- Jan 2016
- First submitted
- 27 Jun 2008
- Last updated
- 8 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 24630419
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00708201
- Acronym / sponsor ID
- 3753-002
- Conditions
- Postoperative Ileus
- Keywords
- ileus, POI
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 280 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Study start
- Mar 2009
- Primary completion
- Jan 2012 (actual)
- Study completion
- Jan 2012 (actual)
- First posted
- 2 Jul 2008 (estimated)
- Results
- Posted 2 Jul 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Alvimopan | Experimental | Drug: Alvimopan12 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 |
| Placebo | Placebo comparator | Drug: Placebo300 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AlvimopanAlso: ADL2698, Entereg | Drug | Alvimopan |
| Placebo | Drug | Placebo |
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
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)
8 secondary outcomes
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
Mean Time to Discharge Order Written (DOW) Using KM Estimates
Time frame: Day of surgery (Day 0) up to 10 days in hospital
Postoperative Length of Stay (LOS)
Time frame: Day of surgery (Day 0) to the day of hospital DOW
Percentage of Participants Considered Postoperative LOS Responders
Time frame: Day of surgery (Day 0) up to 7 days after surgery
Percentage of Participants With Postoperative Morbidity (POM)
Time frame: During hospitalization or within 7 days 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
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
Percentage of Participants With Blinded Adjudicated Cardiovascular (CV) Events
Time frame: Baseline to 30 days post discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24630419Lee 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lee Techner, DPM study director
Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
20 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Alvimopan in people with Postoperative Ileus, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 20 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00708201, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2016.