Ileus
Conditions
Keywords
HIPEC, peritoneal carcinomatosis
Brief summary
The purpose of this study is to investigate the ability of alvimopan to reduce the time to return of bowel function in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Half of the participants will receive alvimopan or and half will receive placebo immediately before and for up to seven days after surgery.
Detailed description
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a surgical procedure to treat cancer that has spread to the lining of the abdominal cavity (peritoneal metastases). It is associated with a prolonged time for return of bowel function after surgery. Alvimopan is a drug used to speed up the time for return of bowel function after surgery. It works by blocking the opioid receptors in the gastrointestinal tract, which normally slow down bowel function in patients receiving postoperative opioid pain medication. It has not previously been tested in patients undergoing CRS/HIPEC.
Interventions
DRUGAlvimopan
alvimopan pill
DRUGPlacebo
placebo pill
Sponsors
University of California, San Diego
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to understand and the willingness to sign a written informed consent. * Scheduled to undergo open (non-minimally invasive) CRS/HIPEC. * Scheduled to receive postoperative pain management with intravenous opioids. * Age \> 18 years. * Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. * Women of child-bearing potential with negative pregnancy test prior to initiating study drug dosing.
Exclusion criteria
* Greater than 7 days of consecutive opioid use immediately prior to scheduled surgery. * Child-Pugh Class C hepatic impairment. * End-stage renal disease (GFR \< 15 mL/min/1.73 m2 and/or on peritoneal dialysis or hemodialysis). * Complete mechanical bowel obstruction. * Contraindication or inability to tolerate oral medication postoperatively. * Presence of gastrointestinal ostomy after CRS/HIPEC. * Pancreatic or gastric anastomosis performed during CRS/HIPEC. * History of allergic reactions or hypersensitivity attributed to compounds of similar chemical or biologic composition as alvimopan at the treating investigators discretion. * Severe or uncontrolled medical disorder that would, in the investigator's opinion, impair ability to receive study treatment (i.e. uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements). * History of myocardial infarction in the 12 months prior to scheduled surgery. * Pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Return of Upper and Lower GI Function | from surgery to discharge (generally no longer than two weeks) | The later of the time from surgery that the participant first tolerates solid food and the time that the participant first passes a bowel movement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prolonged Ileus | from surgery to discharge (generally no longer than two weeks) | The proportion of patients who do not pass flatus or bowel movement greater than 7 days from the time of surgery. |
| Time to Return of Bowel Function Components | from surgery to discharge (generally no longer than two weeks) | The time from surgery until: * The time to first flatus * The time to first bowel movement * The time to tolerance of solid food |
| Time to Discharge | from surgery to discharge (generally no longer than two weeks) | The time from surgery until discharge order written. |
| Serious Adverse Events | up to 30 days from surgery | The number and proportion of serious adverse events. |
| Subgroup Analyses | up to 30 days from surgery | All primary and secondary outcomes will be measured in the following subgroups: * 0 vs. 1 or greater bowel anastomoses * 0 vs. 1 or greater visceral resections * high vs. low amount of postoperative opioid use * epidural vs. no epidural |
Countries
United States
Participant flow
Pre-assignment details
84 participants were enrolled and randomized (constitute the safety population). All participants must later meet surgical eligibility for final allocation and analysis (n=62).
Participants by arm
| Arm | Count |
|---|---|
| Alvimopan Alvimpan Arm | 30 |
| Placebo Placebo Arm | 32 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible by operative criteria | 12 | 10 |
Baseline characteristics
| Characteristic | Alvimopan | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 53 years | 61 years | 57 years |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 22 Participants | 12 Participants | 34 Participants |
| Sex: Female, Male Male | 8 Participants | 20 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 42 |
| other Total, other adverse events | 35 / 42 | 37 / 42 |
| serious Total, serious adverse events | 7 / 42 | 5 / 42 |
Outcome results
Primary
Time to Return of Upper and Lower GI Function
The later of the time from surgery that the participant first tolerates solid food and the time that the participant first passes a bowel movement.
Time frame: from surgery to discharge (generally no longer than two weeks)
Population: Study was terminated early, preliminary data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alvimopan | Time to Return of Upper and Lower GI Function | 117 hours |
| Placebo | Time to Return of Upper and Lower GI Function | 152 hours |
Secondary
Prolonged Ileus
The proportion of patients who do not pass flatus or bowel movement greater than 7 days from the time of surgery.
Time frame: from surgery to discharge (generally no longer than two weeks)
Population: Study was terminated early, preliminary data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alvimopan | Prolonged Ileus | 3 Participants |
| Placebo | Prolonged Ileus | 12 Participants |
Secondary
Serious Adverse Events
The number and proportion of serious adverse events.
Time frame: up to 30 days from surgery
Population: From Safety population (n=84) Study was terminated early, preliminary data
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Alvimopan | Serious Adverse Events | 7 Participants |
| Placebo | Serious Adverse Events | 5 Participants |
Secondary
Subgroup Analyses
All primary and secondary outcomes will be measured in the following subgroups: * 0 vs. 1 or greater bowel anastomoses * 0 vs. 1 or greater visceral resections * high vs. low amount of postoperative opioid use * epidural vs. no epidural
Time frame: up to 30 days from surgery
Population: Study was terminated early, data was not collected.
Secondary
Time to Discharge
The time from surgery until discharge order written.
Time frame: from surgery to discharge (generally no longer than two weeks)
Population: Study was terminated early, preliminary data
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alvimopan | Time to Discharge | 188 hours |
| Placebo | Time to Discharge | 190 hours |
Secondary
Time to Return of Bowel Function Components
The time from surgery until: * The time to first flatus * The time to first bowel movement * The time to tolerance of solid food
Time frame: from surgery to discharge (generally no longer than two weeks)
Population: Study was terminated early, preliminary data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Alvimopan | Time to Return of Bowel Function Components | Time to tolerance of solid food | 117 hours |
| Alvimopan | Time to Return of Bowel Function Components | Time to first flatus | 64 hours |
| Alvimopan | Time to Return of Bowel Function Components | Time to first BM | 67 hours |
| Placebo | Time to Return of Bowel Function Components | Time to first flatus | 79 hours |
| Placebo | Time to Return of Bowel Function Components | Time to first BM | 89 hours |
| Placebo | Time to Return of Bowel Function Components | Time to tolerance of solid food | 149 hours |