Trial Outcomes & Findings for Analgesic Efficacy of Repeated Doses of Intravenous (IV) Acetaminophen in Post-operative Pediatric Spine Fusion Patients (NCT NCT01394718)

Results Overview

Total opiate requirement was monitored 24 hours post-operatively. Morphine and hydromorphone measurements were totaled and recorded in mg/kg/day of morphine equivalents.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

67 participants

Primary outcome timeframe

24 hours

Results posted on

2016-04-18

Participant Flow

All children of ages 10-18 undergoing posterior spine fusion surgery for idiopathic or neuromuscular scoliosis between July 2011 and May 2014 were eligible for inclusion.

281 subjects were screened, 125 approached for consent/assent and 67 consented/assented. Of the initial 67 subjects, 1 was withdrawn by the clinical team, 1 patient's surgery was cancelled, 2 were withdrawn by the family, and 3 were deemed ineligible after consent were removed from the study.

Participant milestones

Participant milestones
Measure	Saline Placebo Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Placebo: Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Intravenous Acetaminophen Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Intravenous Acetaminophen: Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.
Overall Study STARTED	30	30
Overall Study COMPLETED	28	29
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Saline Placebo Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Placebo: Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Intravenous Acetaminophen Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Intravenous Acetaminophen: Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.
Overall Study Met protocol-specific stopping criteria	2	1

Baseline Characteristics

Analgesic Efficacy of Repeated Doses of Intravenous (IV) Acetaminophen in Post-operative Pediatric Spine Fusion Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Saline Placebo n=28 Participants Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Placebo: Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Intravenous Acetaminophen n=29 Participants Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Intravenous Acetaminophen: Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.	Total n=57 Participants Total of all reporting groups
Age, Continuous	14.43 years STANDARD_DEVIATION 1.69 • n=5 Participants	14.17 years STANDARD_DEVIATION 1.87 • n=7 Participants	14.30 years STANDARD_DEVIATION 1.77 • n=5 Participants
Sex: Female, Male Female	19 Participants n=5 Participants	25 Participants n=7 Participants	44 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants	29 participants n=7 Participants	57 participants n=5 Participants
Weight	59.79 kilograms (kg) STANDARD_DEVIATION 13.69 • n=5 Participants	53.44 kilograms (kg) STANDARD_DEVIATION 11.32 • n=7 Participants	56.56 kilograms (kg) STANDARD_DEVIATION 12.83 • n=5 Participants
Surgery Duration	5.21 hours (hr) STANDARD_DEVIATION 1.03 • n=5 Participants	5.09 hours (hr) STANDARD_DEVIATION 1.14 • n=7 Participants	5.15 hours (hr) STANDARD_DEVIATION 1.08 • n=5 Participants
Estimated Blood Loss (EBL)	775 milliliter (ml) n=5 Participants	600 milliliter (ml) n=7 Participants	700 milliliter (ml) n=5 Participants
Intra-operative methadone	0.1 milligrams/kilograms (mg/kg) n=5 Participants	0.1 milligrams/kilograms (mg/kg) n=7 Participants	0.1 milligrams/kilograms (mg/kg) n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: Subjects were deemed evaluable if a minimum of 24 hours of data was collected post-operatively, with receipt of at least four doses of study drug, prior to study withdrawal or unblinding, with T0 (time zero) being time of administration of first dose of either treatment drug or placebo.

Total opiate requirement was monitored 24 hours post-operatively. Morphine and hydromorphone measurements were totaled and recorded in mg/kg/day of morphine equivalents.

Outcome measures

Outcome measures
Measure	Saline Placebo n=28 Participants Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Placebo: Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Intravenous Acetaminophen n=29 Participants Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Intravenous Acetaminophen: Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.
Total Opiate Requirement	1.19 mg/kg Standard Deviation 0.43	1.01 mg/kg Standard Deviation 0.32

SECONDARY outcome

Timeframe: 24 hours

Population: Subjects were deemed evaluable if a minimum of 24 hours of data was collected post-operatively, with receipt of at least four doses of study drug, prior to study withdrawal or unblinding, with T0 (time zero) being time of administration of first dose of either treatment drug or placebo

Pain Scores were monitored using the numeric pain assessment scale in both treatment arms of the study and recorded and averaged for the first 24 hours after initial intra-operative dose of study drug. The numeric pain assessment scale is a verbal self-reported pain assessment that ranges between 1 (no pain) to 10 (worst pain imaginable).

Outcome measures

Outcome measures
Measure	Saline Placebo n=28 Participants Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Placebo: Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Intravenous Acetaminophen n=29 Participants Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Intravenous Acetaminophen: Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.
Average Pain Score	4.53 units on a scale Standard Deviation 2.02	4.62 units on a scale Standard Deviation 1.99

SECONDARY outcome

Timeframe: 24 hours

Population: Subjects were deemed evaluable if a minimum of 24 hours of data was collected post-operatively, with receipt of at least four doses of study drug, prior to study withdrawal or unblinding, with T0 (time zero) being time of administration of first dose of either treatment drug or placebo

Nausea scores were recorded by the nursing staff approximately 4 times over the first 24 hours and then averaged for the 24 hour period. Nausea Scores range from 1 (none) to 4 (severe).

Outcome measures

Outcome measures
Measure	Saline Placebo n=28 Participants Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Placebo: Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Intravenous Acetaminophen n=29 Participants Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Intravenous Acetaminophen: Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.
Average Nausea Score	1.2 units on a scale Interval 1.0 to 2.5	1.0 units on a scale Interval 1.0 to 2.6

SECONDARY outcome

Timeframe: 24 hours

Population: Subjects were deemed evaluable if a minimum of 24 hours of data was collected post-operatively, with receipt of at least four doses of study drug, prior to study withdrawal or unblinding, with T0 (time zero) being time of administration of first dose of either treatment drug or placebo

Pruritus scores were recorded by the nursing staff approximately 4 times over the first 24 hours and then averaged for the 24 hour period. Pruritus scores range from 1 (none) to 3 (intolerable).

Outcome measures

Outcome measures
Measure	Saline Placebo n=28 Participants Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Placebo: Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Intravenous Acetaminophen n=29 Participants Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses). Intravenous Acetaminophen: Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.
Average Pruritus Score	1.0 units on a scale Interval 1.0 to 2.5	1 units on a scale Interval 1.0 to 2.0

Adverse Events

Saline Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intravenous Acetaminophen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Athena Zuppa, MD, MSCE

Children's Hospital of Philadelphia

Phone: 267-426-7359

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place