Constipation
Conditions
Brief summary
Constipation is a known complication of the postoperative period after spinal surgery, where prescription pain medicines called opioids are traditionally used in high doses for the treatment of surgery-related pain. The goal of this study is to determine the effectiveness of Movantik (naloxegol)-a FDA-approved drug used to treat constipation that is caused by opioids-in preventing constipation in patients undergoing spinal fusion surgery at MGH.
Detailed description
We conducted a randomized, double-blind, placebo-controlled trial at a single, academic tertiary center (Massachusetts General Hospital, Boston, MA) from 2017 to 2018. Adult male and female patients between the ages of 18 and 80 who were planned to undergo non-urgent, elective posterior-approach spinal fusion surgeries by the Department of Neurosurgery were eligible for inclusion. Of note, patients with preexisting opioid and/or laxative use were still considered eligible and patients were not stratified according to these characteristics. Once a surgeon and the patient made a joint decision to proceed with elective, posterior spinal fusion surgery, patients would be approached by study personnel, with all eligible patients recruited independently of their surgeon to ensure no conflict of interest. After informed consent, eligible patients provided baseline demographic information including age, sex, race, pre-operative laxative use, and pre-operative opioid use. In addition, subjects completed a Bowel Function Index (BFI), a validated measure of opioid-induced constipation.10 Patients were not instructed to alter their daily regimen from time of consent to initiation of the study. On the day prior to scheduled surgery, clinical research pharmacy staff randomized subjects in a 1:1 ratio. With the exception of the pharmacist preparing the study drug or placebo, who was unaffiliated with the investigators or study sponsor, the individual treatment assignment was unknown to study staff, patients, sponsors, and clinical treatment teams. Upon completion of surgery, post operative care unit nurses administered 25 mg of oral naloxegol (12.5 mg for creatinine clearance of \<60 mL/min) or an identical placebo within 2 hours of arrival in the recovery room post-operatively and then every 24 hours thereafter
Interventions
DRUGMOVANTIK™ (naloxegol)
DRUGSugar Pill
Sponsors
AstraZeneca
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients between the ages of 18 and 75 years undergoing non-urgent, elective spinal fusion at Massachusetts General Hospital who are admitted to the neurosurgery floor from the operating room
Exclusion criteria
* Patients who are taken to the operating room from another inpatient floor or service (already hospitalized prior to surgery) * Patients with evidence of bowel obstruction * Patients unable to take oral medications by mouth or by enteric feeding tube (gastrostomy or jejunostomy) * Patients with a documented or potential allergy or adverse reaction to Movantik (naloxegol) from outpatient use * Patients currently taking Movantik (naloxegol) in the outpatient setting * Patients with a preoperative diagnosis of irritable bowel syndrome (IBS) obtained via Rome III questionnaire on screening * Patients with disruptions to the blood-brain barrier (eg, multiple sclerosis, recent brain injury, Alzheimer's disease, and uncontrolled epilepsy) * Patients with a history of cancer. * Patients concomitantly using strong CYP3A4 inhibitors (eg, clarithromycin, ketoconazole), strong CYP3A4 inducers and other opioid antagonists. * Patients with severe hepatic impairment. * Patients with a previous history of or risk of bowel perforation. * Patients with a post-op regional anesthetic technique employed like a continuous epidural or spinal. * Patients for which local anesthetics will be placed in the wound.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Post-operative Spontaneous Bowel Movement | through study completion, an average of 6 days | The primary endpoint of the study was time to first post-operative bowel movement, as defined by the first spontaneous bowel movement reported by nursing staff after transfer from the surgical suite to the inpatient floor. A bowel movement was defined as the spontaneous passage of one tablespoon or more of liquid or solid stool (excluding flatus), which could be measured and verified by nursing staff. Time was measured in hours post-operatively with the starting time point marked at the end of the surgical procedure. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Rescue Laxative Medication Use During Hospitalization | upon discharge from hospital, an average of 5 days | The use of a rescue laxative medication is defined as the administration of an additional bowel medication due to a decision by the clinical treatment team that the subject suffered from constipation and required a rescue bowel medication. Of note, this medication did not include the study drug, placebo, or the standing laxative orders used in all patient (docusate and sennosides). By definition, a rescue medication could only be given before a subject's first bowel movement or discharge |
| Length of Stay | through study completion, an average of 6 days | — |
| Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index | through study completion, an average of 6 days | BFI normal reference range is 0-28.8 (on a scale of 100 for all 3 items summed and divided by 3). Higher scores mean a worse outcome. |
| Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale. | upon discharge from hospital, an average of 5 days | Patients completed a bowel satisfaction questionnaire on day of discharge. 5-point Likert scale, Very dissatisfied to Very satisfied. Higher scores mean a better outcome. |
| Number of Participants That Experienced Diarrhea | through study completion, an average of 6 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MOVANTIK™ (Naloxegol) Subjects in the treatment group will be administered MOVANTIK™ (naloxegol) 25 mg tablet or placebo once daily beginning 2 hours after the completion of their surgery until their discharge from the hospital (variable timing). Subjects with renal impairments (creatine clearance rate of less than 60 mL/min) will receive a 12.5 mg dose tablet of naloxegol in place of the 25 mg dose as advised by FDA guidelines. For patients who are unable to swallow the tablet whole, the tablet can be crushed and given orally or administered via nasogastric tube.
MOVANTIK™ (naloxegol) | 28 |
| Sugar Pill Matching placebo consists of an inert mixture supplied by AstraZeneca in identical-appearing tablets. Subjects in the placebo group will be administered a placebo tablet once daily beginning 2 hours after the completion of their surgery until their discharge from the hospital (variable timing).
Sugar Pill | 24 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Did not undergo posterior spinal fusion | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Sugar Pill | Total | MOVANTIK™ (Naloxegol) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 13 Participants | 29 Participants | 16 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 23 Participants | 12 Participants |
| Age, Continuous | 64.6 years STANDARD_DEVIATION 8.7 | 64.6 years STANDARD_DEVIATION 9.1 | 64.6 years STANDARD_DEVIATION 9.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 47 Participants | 25 Participants |
| Region of Enrollment United States | 24 participants | 52 participants | 28 participants |
| Sex: Female, Male Female | 13 Participants | 26 Participants | 13 Participants |
| Sex: Female, Male Male | 11 Participants | 26 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 24 |
| other Total, other adverse events | 1 / 28 | 1 / 24 |
| serious Total, serious adverse events | 0 / 28 | 1 / 24 |
Outcome results
Primary
Time to First Post-operative Spontaneous Bowel Movement
The primary endpoint of the study was time to first post-operative bowel movement, as defined by the first spontaneous bowel movement reported by nursing staff after transfer from the surgical suite to the inpatient floor. A bowel movement was defined as the spontaneous passage of one tablespoon or more of liquid or solid stool (excluding flatus), which could be measured and verified by nursing staff. Time was measured in hours post-operatively with the starting time point marked at the end of the surgical procedure.
Time frame: through study completion, an average of 6 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MOVANTIK™ (Naloxegol) | Time to First Post-operative Spontaneous Bowel Movement | 91 hours |
| Sugar Pill | Time to First Post-operative Spontaneous Bowel Movement | 94 hours |
Secondary
Length of Stay
Time frame: through study completion, an average of 6 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOVANTIK™ (Naloxegol) | Length of Stay | 106 hours | Standard Deviation 44.7 |
| Sugar Pill | Length of Stay | 133 hours | Standard Deviation 31.6 |
Secondary
Number of Participants That Experienced Diarrhea
Time frame: through study completion, an average of 6 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MOVANTIK™ (Naloxegol) | Number of Participants That Experienced Diarrhea | 0 Participants |
| Sugar Pill | Number of Participants That Experienced Diarrhea | 1 Participants |
Secondary
Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale.
Patients completed a bowel satisfaction questionnaire on day of discharge. 5-point Likert scale, Very dissatisfied to Very satisfied. Higher scores mean a better outcome.
Time frame: upon discharge from hospital, an average of 5 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOVANTIK™ (Naloxegol) | Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale. | 3.4 score on a scale | Standard Deviation 1.3 |
| Sugar Pill | Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale. | 3.3 score on a scale | Standard Deviation 1.4 |
Secondary
Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index
BFI normal reference range is 0-28.8 (on a scale of 100 for all 3 items summed and divided by 3). Higher scores mean a worse outcome.
Time frame: through study completion, an average of 6 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MOVANTIK™ (Naloxegol) | Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index | 14.3 score on a scale | Standard Deviation 19.8 |
| Sugar Pill | Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index | 16.9 score on a scale | Standard Deviation 21.5 |
Secondary
Time to Rescue Laxative Medication Use During Hospitalization
The use of a rescue laxative medication is defined as the administration of an additional bowel medication due to a decision by the clinical treatment team that the subject suffered from constipation and required a rescue bowel medication. Of note, this medication did not include the study drug, placebo, or the standing laxative orders used in all patient (docusate and sennosides). By definition, a rescue medication could only be given before a subject's first bowel movement or discharge
Time frame: upon discharge from hospital, an average of 5 days
Population: Patients who received rescue laxative medication while hospitalized.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MOVANTIK™ (Naloxegol) | Time to Rescue Laxative Medication Use During Hospitalization | 70 hours |
| Sugar Pill | Time to Rescue Laxative Medication Use During Hospitalization | 75 hours |