Trial Outcomes & Findings for Naloxegol for the Prevention of Constipation in Postoperative Spinal Surgery Patients (NCT NCT02946580)

Last Updated: 2019-09-10

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

53 participants

Primary outcome timeframe

through study completion, an average of 6 days

Results posted on

2019-09-10

Participant Flow

Participant milestones

Participant milestones
Measure	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)	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
Overall Study STARTED	28	25
Overall Study COMPLETED	27	20
Overall Study NOT COMPLETED	1	5

Reasons for withdrawal

Reasons for withdrawal
Measure	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)	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
Overall Study Withdrawal by Subject	1	2
Overall Study Adverse Event	0	2
Overall Study Did not undergo posterior spinal fusion	0	1

Baseline Characteristics

One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	MOVANTIK™ (Naloxegol) n=28 Participants 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)	Sugar Pill n=24 Participants 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 n=52 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.	0 Participants n=7 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.	0 Participants n=5 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.	11 Participants n=7 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.	23 Participants n=5 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.
Age, Categorical >=65 years	16 Participants n=5 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.	13 Participants n=7 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.	29 Participants n=5 Participants • One patient out of the 53 enrolled in our study did not undergo posterior fusion surgery and thus was excluded from our analysis.
Age, Continuous	64.6 years STANDARD_DEVIATION 9.4 • n=5 Participants	64.6 years STANDARD_DEVIATION 8.7 • n=7 Participants	64.6 years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	25 Participants n=5 Participants	22 Participants n=7 Participants	47 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants	24 participants n=7 Participants	52 participants n=5 Participants

PRIMARY outcome

Timeframe: through study completion, an average of 6 days

Outcome measures

Outcome measures
Measure	MOVANTIK™ (Naloxegol) n=28 Participants 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)	Sugar Pill n=24 Participants 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
Time to First Post-operative Spontaneous Bowel Movement	91 hours Interval 22.0 to 186.0	94 hours Interval 43.0 to 152.0

SECONDARY outcome

Timeframe: upon discharge from hospital, an average of 5 days

Population: Patients who received rescue laxative medication while hospitalized.

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

Outcome measures

Outcome measures
Measure	MOVANTIK™ (Naloxegol) n=15 Participants 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)	Sugar Pill n=10 Participants 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
Time to Rescue Laxative Medication Use During Hospitalization	70 hours Interval 17.1 to 183.0	75 hours Interval 46.0 to 96.9

SECONDARY outcome

Timeframe: through study completion, an average of 6 days

Outcome measures

Outcome measures
Measure	MOVANTIK™ (Naloxegol) n=28 Participants 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)	Sugar Pill n=24 Participants 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
Length of Stay	106 hours Standard Deviation 44.7	133 hours Standard Deviation 31.6

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MOVANTIK™ (Naloxegol) n=28 Participants 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)	Sugar Pill n=24 Participants 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
Patient's Satisfaction With Their Bowels by Use of the Bowel Function Index	14.3 score on a scale Standard Deviation 19.8	16.9 score on a scale Standard Deviation 21.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	MOVANTIK™ (Naloxegol) n=28 Participants 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)	Sugar Pill n=24 Participants 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
Patient's Satisfaction With Their Bowels at Discharge Using a 5-point Likert Scale.	3.4 score on a scale Standard Deviation 1.3	3.3 score on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: through study completion, an average of 6 days

Outcome measures

Outcome measures
Measure	MOVANTIK™ (Naloxegol) n=28 Participants 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)	Sugar Pill n=24 Participants 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
Number of Participants That Experienced Diarrhea	0 Participants	1 Participants

Adverse Events

MOVANTIK™ (Naloxegol)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Sugar Pill

Serious events: 1 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	MOVANTIK™ (Naloxegol) n=28 participants at risk 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)	Sugar Pill n=24 participants at risk 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
Gastrointestinal disorders Ileus	0.00% 0/28 • 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.	4.2% 1/24 • Number of events 1 • 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.

Other adverse events

Other adverse events
Measure	MOVANTIK™ (Naloxegol) n=28 participants at risk 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)	Sugar Pill n=24 participants at risk 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
Gastrointestinal disorders Constipation resulting in re-admission to Emergency Department	3.6% 1/28 • Number of events 1 • 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.	0.00% 0/24 • 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.
Gastrointestinal disorders Diarrhea	0.00% 0/28 • 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.	4.2% 1/24 • Number of events 1 • 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.

Additional Information

Dr. Kyle Staller

Massachusetts General Hospital

Phone: 617-724-7556

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place