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| ID | Type | Description | Link |
|---|---|---|---|
| ESR-15-11338, D3820L00008 | Other Grant/Funding Number | AstraZeneca |
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Slow recruitment and inability to extend funding.
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MOVANTIK™ (naloxegol) | Experimental | 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. |
|
| Sugar pill | Placebo Comparator | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MOVANTIK™ (naloxegol) | Drug |
| ||
| Sugar Pill |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | through study completion, an average of 6 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kyle Staller, MD, MPH | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02114 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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) |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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) |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis. |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Inter-Quartile Range | hours | through study completion, an average of 6 days |
|
Adverse event data was collected throughout hospitalization and 3 days after discharge, or until first post-operative bowel movement if it occurred >3 days after discharge, up to 2 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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) |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Ileus | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Constipation resulting in re-admission to Emergency Department | Gastrointestinal disorders | Systematic Assessment | Admission to emergency department on day 4 post discharge due to constipation |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Kyle Staller | Massachusetts General Hospital | 617-724-7556 | kstaller@mgh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 2, 2019 | Aug 20, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003248 | Constipation |
| ID | Term |
|---|---|
| D012817 | Signs and Symptoms, Digestive |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C000589308 | naloxegol |
| D000073893 | Sugars |
| ID | Term |
|---|---|
| D002241 | Carbohydrates |
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|
| upon discharge from hospital, an average of 5 days |
| Length of Stay | through study completion, an average of 6 days |
| 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. | through study completion, an average of 6 days |
| 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. | upon discharge from hospital, an average of 5 days |
| Number of Participants That Experienced Diarrhea | through study completion, an average of 6 days |
| Did not undergo posterior spinal fusion |
|
| BG001 | 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 |
| BG002 | Total | Total of all reporting groups |
| Count of Participants |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | 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 |
|
|
| 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 | Patients who received rescue laxative medication while hospitalized. | Posted | Mean | Full Range | hours | upon discharge from hospital, an average of 5 days |
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| Secondary | Length of Stay | Posted | Mean | Standard Deviation | hours | through study completion, an average of 6 days |
|
|
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| 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. | Posted | Mean | Standard Deviation | score on a scale | through study completion, an average of 6 days |
|
|
|
| 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. | Posted | Mean | Standard Deviation | score on a scale | upon discharge from hospital, an average of 5 days |
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| Secondary | Number of Participants That Experienced Diarrhea | Posted | Count of Participants | Participants | through study completion, an average of 6 days |
|
|
|
| 0 |
| 28 |
| 0 |
| 28 |
| 1 |
| 28 |
| EG001 | 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 | 0 | 24 | 1 | 24 | 1 | 24 |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
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