Naloxegol for the Prevention of Constipation in Postoperative Spinal Surgery Patients

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02946580
• Collaborator: AstraZeneca (Industry)
• Enrollment: 53
• Location: 1
• Arms: 2
• Duration (Months): 13
• Patients Per Site Per Month: 4.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Constipation	Drug: MOVANTIK™ (naloxegol); Drug: Sugar Pill	Phase 4

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Prevention
• Official Title: A Double-blind, Randomized, Placebo-controlled Trial of Naloxegol for Prevention of Post-operative Constipation in Spinal Surgery Patients
• Study Start Date: Jan 1, 2017
• Actual Primary Completion Date: Feb 1, 2018
• Actual Study Completion Date: Feb 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: MOVANTIK™ (naloxegol)
Placebo Comparator: 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).	Drug: Sugar Pill

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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

2. Length of Stay [through study completion, an average of 6 days]

3. 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.

4. 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.

5. Number of Participants That Experienced Diarrhea [through study completion, an average of 6 days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital
• AstraZeneca

Investigators

• Principal Investigator: Kyle Staller, MD, MPH, Massachusetts General Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 2, 2019

More Information

Publications

None provided.

• Responsible Party: Kyle Staller, MD, MPH, Principle Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02946580
• Other Study ID Numbers: 2016P001847; ESR-15-11338, D3820L00008
• First Posted: Oct 27, 2016
• Last Update Posted: Sep 10, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Constipation; Naloxegol

Study Results

Participant Flow

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill
Arm/Group Description	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)	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
Period Title: Overall Study
STARTED	28	25
COMPLETED	27	20
NOT COMPLETED	1	5

Baseline Characteristics

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill	Total
Arm/Group Description	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)	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	Total of all reporting groups
Overall Participants	28	24	52
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 42.9%	11 45.8%	23 44.2%
>=65 years	16 57.1%	13 54.2%	29 55.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.6 (9.4)	64.6 (8.7)	64.6 (9.1)
Sex: Female, Male (Count of Participants)
Female	13 46.4%	13 54.2%	26 50%
Male	15 53.6%	11 45.8%	26 50%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 7.1%	2 8.3%	4 7.7%
White	25 89.3%	22 91.7%	47 90.4%
More than one race	1 3.6%	0 0%	1 1.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	28 100%	24 100%	52 100%

Outcome Measures

1. Primary Outcome

Title	Time to First Post-operative Spontaneous Bowel Movement
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill
Arm/Group Description	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)	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
Measure Participants	28	24
Mean (Inter-Quartile Range) [hours]	91	94

2. Secondary Outcome

Title	Time to Rescue Laxative Medication Use During Hospitalization
Description	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

Outcome Measure Data

Analysis Population Description

Patients who received rescue laxative medication while hospitalized.

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill
Arm/Group Description	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)	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
Measure Participants	15	10
Mean (Full Range) [hours]	70	75

3. Secondary Outcome

Title	Length of Stay
Time Frame	through study completion, an average of 6 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill
Arm/Group Description	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)	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
Measure Participants	28	24
Mean (Standard Deviation) [hours]	106 (44.7)	133 (31.6)

4. Secondary Outcome

Title	Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill
Arm/Group Description	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)	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
Measure Participants	28	24
Mean (Standard Deviation) [score on a scale]	14.3 (19.8)	16.9 (21.5)

5. Secondary Outcome

Title	Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill
Arm/Group Description	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)	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
Measure Participants	28	24
Mean (Standard Deviation) [score on a scale]	3.4 (1.3)	3.3 (1.4)

6. Secondary Outcome

Title	Number of Participants That Experienced Diarrhea
Time Frame	through study completion, an average of 6 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	MOVANTIK™ (Naloxegol)	Sugar Pill
Arm/Group Description	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)	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
Measure Participants	28	24
Count of Participants [Participants]	0 0%	1 4.2%

Adverse Events

Time Frame	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.
Arm/Group Title	MOVANTIK™ (Naloxegol)		Sugar Pill
Arm/Group Description	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)		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
All Cause Mortality
	MOVANTIK™ (Naloxegol)		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/24 (0%)
Serious Adverse Events
	MOVANTIK™ (Naloxegol)		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		1/24 (4.2%)
Gastrointestinal disorders
Ileus	0/28 (0%)	0	1/24 (4.2%)	1
Other (Not Including Serious) Adverse Events
	MOVANTIK™ (Naloxegol)		Sugar Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/28 (3.6%)		1/24 (4.2%)
Gastrointestinal disorders
Constipation resulting in re-admission to Emergency Department	1/28 (3.6%)	1	0/24 (0%)	0
Diarrhea	0/28 (0%)	0	1/24 (4.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.