Constipation
Conditions
Brief summary
The Investigator has chosen to study the reconstructive spinal surgery patient population because it is believed that the use of alvimopan in these patients at the University of Virginia will give the scientific community significant insight into the broader applicability of this drug into other surgical populations, the impact of this drug on the perception of pain (as opposed to simply the consumption of opioids), and its impact on total hospital charges, resource utilization, and functional outcomes.
Detailed description
Pain control following major spine surgery is difficult to achieve. Opiates are often necessary in high doses, and may be associated with significant side effects. Such side effects may include urinary retention, altered mental status, depressed respiratory drive, and constipation, and may lead to reduced nutritional intake in the postoperative period. Importantly, post-operative nutrition may impact the incidence of complications following spine surgery.1 Alvimopan is a peripheral-acting opiate antagonist designed to decrease the gastrointestinal complications of perioperative systemic opioid administration. Pain control following major spine surgery is difficult to achieve. Opiates are often necessary in high doses, and may be associated with significant side effects including constipation. Alvimopan is a drug approved by the Food and Drug Administration (FDA) and is used to help the bowel recover more quickly in patients who are having bowel surgery, so that they can eat solid foods and have regular bowel movements. Alvimopan is in a class of medications called peripherally acting mu-opioid receptor antagonists. It works by protecting the bowel from the constipation effects of opioid (narcotic) medications that are used to treat pain after surgery. The purpose of this study is to determine if the use of alvimopan in major spine surgery reduces the time to first bowel movement. By assessing the use of alvimopan in reconstructive spinal surgery patients, researchers hope to give the scientific community insight into the broader use of this drug in other surgical populations, as well as gathering information on the impact of hospital charges and overall post-operative patient satisfaction.
Interventions
DRUGAlvimopan
Alviimopan 12 mg twice daily up to 15 doses
DRUGPlacebo
Placebo twice daily up to 15 doses
Sponsors
Merck Sharp & Dohme LLC
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Major spine surgery scheduled as part of clinical care * 18-80 years
Exclusion criteria
* More than three doses of any opioid within one week of surgery * Pregnancy * Prisoners * Unable to provide consent * Emergency surgery * Chronic kidney disease stage 5 (GFR \< 15 ml/min) * Severe hepatic impairment * Recent myocardial infarction (within the last 3 months)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Bowel Movement | Time to event( up to 7 days); From date of day of surgery until the date of first documented bowel movement | time to first bowel movement after surgery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Resumption of PO Intake | time to event ( up to 7 days); From date of day of surgery until the date of first documented PO intake | time to resumption oral intake after surgery |
Countries
United States
Participant flow
Recruitment details
Forty-nine opioid-naive participants undergoing spine surgery between 2016 and 2018 with neurological monitoring were screened and included for eligibility. A total of 24 patients were assigned to the active group and 25 were assigned to the placebo group. One patient from the alvimopan group had surgery canceled, and thus was excluded from further analysis. In the placebo arm, 4 patients were recruited but withdrew from the study.
Pre-assignment details
All 49 consented participants were assigned to an arm.
Participants by arm
| Arm | Count |
|---|---|
| Alvimopan 12 mg alvimopan twice a day (either by mouth or by (NG) nasogastric tube) for up to seven days post-operatively, or until the time of discharge, whichever occurs first, to a maximum of 15 doses.
Alvimopan: Alviimopan 12 mg twice daily up to 15 doses | 23 |
| Placebo Placebo twice a day (either by mouth or by (NG) nasogastric tube) for up to seven days post-operatively, or until the time of discharge, whichever occurs first, to a maximum of 15 doses.
Placebo: Placebo twice daily up to 15 doses | 20 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 4 |
Baseline characteristics
| Characteristic | Alvimopan | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 11 Participants | 24 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants | 9 Participants | 19 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 14 Participants | 9 Participants | 23 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 20 |
| other Total, other adverse events | 0 / 23 | 0 / 20 |
| serious Total, serious adverse events | 0 / 23 | 0 / 20 |
Outcome results
Primary
Time to First Bowel Movement
time to first bowel movement after surgery
Time frame: Time to event( up to 7 days); From date of day of surgery until the date of first documented bowel movement
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Alvimopan | Time to First Bowel Movement | 50 hours |
| Placebo | Time to First Bowel Movement | 64 hours |
Secondary
Time to Resumption of PO Intake
time to resumption oral intake after surgery
Time frame: time to event ( up to 7 days); From date of day of surgery until the date of first documented PO intake
Population: Placebo vs. Alvimopan
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Alvimopan | Time to Resumption of PO Intake | 17 hours |
| Placebo | Time to Resumption of PO Intake | 14.5 hours |