Trial Outcomes & Findings for A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients (NCT NCT01635101)
NCT ID: NCT01635101
Last Updated: 2020-01-21
Results Overview
Total micrograms per kilogram (µg/kg) of rescue opioid used during the same 24 hours the subject is on study medication
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
197 participants
Primary outcome timeframe
in 24 hours
Results posted on
2020-01-21
Participant Flow
Of 215 participants screened, 197 were actually enrolled and received study drug
Participant milestones
| Measure |
Low Dose Acetaminophen
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
Participants receive matching placebo administered intravenously for 24 hours
|
|---|---|---|---|
|
Overall Study
STARTED
|
61
|
67
|
69
|
|
Overall Study
Safety Population
|
61
|
67
|
69
|
|
Overall Study
Modified Intent to Treat (mITT)
|
61
|
67
|
69
|
|
Overall Study
Pharmacokinetics Evaluable Population
|
50
|
59
|
58
|
|
Overall Study
COMPLETED
|
52
|
55
|
52
|
|
Overall Study
NOT COMPLETED
|
9
|
12
|
17
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients
Baseline characteristics by cohort
| Measure |
Low Dose Acetaminophen
n=61 Participants
Participants received a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=67 Participants
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=69 Participants
Participants receive matching placebo for 24 hours
|
Total
n=197 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
All Participants · Neonates (birth to ≤ 28 days)
|
13 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
13 Participants
n=5 Participants
|
38 Participants
n=4 Participants
|
|
Age, Customized
All Participants · Younger infants (≥ 29 days to < 6 mos)
|
16 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
54 Participants
n=4 Participants
|
|
Age, Customized
All Participants · Intermediate aged infants (≥ 6 mos to <12 mos)
|
18 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
|
Age, Customized
All Participants · Older infants (≥12 mos to <24 mos)
|
14 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
50 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
27 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
70 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
44 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
43 Participants
n=5 Participants
|
127 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
13 Participants
n=4 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
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
12 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
30 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
40 Participants
n=5 Participants
|
49 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
135 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
18 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
61 participants
n=5 Participants
|
67 participants
n=7 Participants
|
69 participants
n=5 Participants
|
197 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: in 24 hoursPopulation: mITT population
Total micrograms per kilogram (µg/kg) of rescue opioid used during the same 24 hours the subject is on study medication
Outcome measures
| Measure |
Low Dose Acetaminophen
n=61 Participants
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=67 Participants
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=69 Participants
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Total Rescue Opioid Consumption
|
166.9 µg/kg
Standard Deviation 225.06
|
179.9 µg/kg
Standard Deviation 193.47
|
180.2 µg/kg
Standard Deviation 184.70
|
SECONDARY outcome
Timeframe: within 24 hoursPopulation: mITT population
Outcome measures
| Measure |
Low Dose Acetaminophen
n=61 Participants
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=67 Participants
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=69 Participants
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Time to First Rescue Medication
|
4.78 hours
Interval 3.15 to 16.32
|
4.76 hours
Interval 2.15 to 10.08
|
3.81 hours
Interval 2.25 to 8.95
|
SECONDARY outcome
Timeframe: within 24 HoursPopulation: Neonates in the mITT population with scores at each data collection time
The LNPS is used for assessing pain intensity in neonates. Scores on the scale run from 0-14. Higher scores mean worse pain.
Outcome measures
| Measure |
Low Dose Acetaminophen
n=13 Participants
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=12 Participants
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=13 Participants
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
at 0 hours
|
0.8 score on a scale
Standard Deviation 1.09
|
0.8 score on a scale
Standard Deviation 1.27
|
1.1 score on a scale
Standard Deviation 1.26
|
|
Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
at 6 hours
|
1.1 score on a scale
Standard Deviation 1.04
|
1.0 score on a scale
Standard Deviation 1.41
|
1.2 score on a scale
Standard Deviation 1.82
|
|
Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
at 12 hours
|
2.2 score on a scale
Standard Deviation 1.92
|
1.8 score on a scale
Standard Deviation 1.76
|
2.0 score on a scale
Standard Deviation 1.83
|
|
Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
at 18 hours
|
1.0 score on a scale
Standard Deviation 1.53
|
1.8 score on a scale
Standard Deviation 1.99
|
0.8 score on a scale
Standard Deviation 0.99
|
|
Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
at 24 hours
|
0.8 score on a scale
Standard Deviation 1.40
|
1.3 score on a scale
Standard Deviation 1.42
|
0.9 score on a scale
Standard Deviation 1.40
|
SECONDARY outcome
Timeframe: within 24 hoursPopulation: Younger Infants in the mITT population with scores at each data collection time
The LNPS is used for assessing pain intensity in younger infants. Scores on the scale run from 0-14. Higher scores mean worse pain.
Outcome measures
| Measure |
Low Dose Acetaminophen
n=16 Participants
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=20 Participants
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=18 Participants
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Summary of Pain Intensity Using the LNPS in Younger Infants
at 0 hours
|
2.1 score on a scale
Standard Deviation 2.85
|
1.5 score on a scale
Standard Deviation 1.85
|
2.2 score on a scale
Standard Deviation 2.05
|
|
Summary of Pain Intensity Using the LNPS in Younger Infants
at 6 hours
|
2.1 score on a scale
Standard Deviation 2.36
|
1.3 score on a scale
Standard Deviation 1.33
|
2.4 score on a scale
Standard Deviation 3.10
|
|
Summary of Pain Intensity Using the LNPS in Younger Infants
at 12 hours
|
2.2 score on a scale
Standard Deviation 2.4
|
1.8 score on a scale
Standard Deviation 1.58
|
1.9 score on a scale
Standard Deviation 1.24
|
|
Summary of Pain Intensity Using the LNPS in Younger Infants
at 18 hours
|
1.6 score on a scale
Standard Deviation 2.25
|
1.7 score on a scale
Standard Deviation 2.06
|
2.1 score on a scale
Standard Deviation 1.44
|
|
Summary of Pain Intensity Using the LNPS in Younger Infants
at 24 hours
|
2.3 score on a scale
Standard Deviation 1.59
|
1.3 score on a scale
Standard Deviation 1.63
|
2.9 score on a scale
Standard Deviation 2.51
|
SECONDARY outcome
Timeframe: within 24 hoursPopulation: Intermediate aged infants in the mITT population with a score at each data collection time
The Face, Leg, Activity, Cry, and Consolability (FLACC) scale is used to assess pain intensity in intermediate aged infants. The scale is scored in a range of 0-10 with 0 representing no pain. A higher score means more pain.
Outcome measures
| Measure |
Low Dose Acetaminophen
n=18 Participants
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=17 Participants
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=20 Participants
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Pain Intensity Using the FLACC Score in Intermediate Aged Infants
at 0 hours
|
0.6 score on a scale
Standard Deviation 1.30
|
1.6 score on a scale
Standard Deviation 2.27
|
1.2 score on a scale
Standard Deviation 2.05
|
|
Pain Intensity Using the FLACC Score in Intermediate Aged Infants
at 6 hours
|
0.7 score on a scale
Standard Deviation 0.83
|
2.1 score on a scale
Standard Deviation 2.71
|
1.4 score on a scale
Standard Deviation 2.59
|
|
Pain Intensity Using the FLACC Score in Intermediate Aged Infants
at 12 hours
|
1.2 score on a scale
Standard Deviation 1.41
|
0.08 score on a scale
Standard Deviation 1.39
|
1.8 score on a scale
Standard Deviation 2.49
|
|
Pain Intensity Using the FLACC Score in Intermediate Aged Infants
at 18 hours
|
1.4 score on a scale
Standard Deviation 2.01
|
0.9 score on a scale
Standard Deviation 1.19
|
0.5 score on a scale
Standard Deviation 0.97
|
|
Pain Intensity Using the FLACC Score in Intermediate Aged Infants
at 24 hours
|
1.4 score on a scale
Standard Deviation 2.29
|
0.9 score on a scale
Standard Deviation 1.56
|
0.3 score on a scale
Standard Deviation 0.65
|
SECONDARY outcome
Timeframe: within 24 hoursPopulation: Older infants in the mITT population with a score at each data collection time
The FLACC scale is used to assess pain intensity in older infants. The scale is scored in a range of 0-10 with 0 representing no pain. A higher score means more pain.
Outcome measures
| Measure |
Low Dose Acetaminophen
n=14 Participants
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=18 Participants
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=18 Participants
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Pain Intensity Using the FLACC Score in Older Infants
at 0 hours
|
2.2 score on a scale
Standard Deviation 2.64
|
1.8 score on a scale
Standard Deviation 2.65
|
1.8 score on a scale
Standard Deviation 2.37
|
|
Pain Intensity Using the FLACC Score in Older Infants
at 6 hours
|
0.5 score on a scale
Standard Deviation 0.90
|
1.2 score on a scale
Standard Deviation 2.07
|
1.5 score on a scale
Standard Deviation 2.42
|
|
Pain Intensity Using the FLACC Score in Older Infants
at 12 hours
|
0.8 score on a scale
Standard Deviation 1.27
|
1.7 score on a scale
Standard Deviation 2.76
|
2.4 score on a scale
Standard Deviation 1.78
|
|
Pain Intensity Using the FLACC Score in Older Infants
at 18 hours
|
1.3 score on a scale
Standard Deviation 1.95
|
0.1 score on a scale
Standard Deviation 0.36
|
1.3 score on a scale
Standard Deviation 2.67
|
|
Pain Intensity Using the FLACC Score in Older Infants
at 24 hours
|
2.0 score on a scale
Standard Deviation 2.59
|
0.8 score on a scale
Standard Deviation 1.12
|
0.1 score on a scale
Standard Deviation 0.29
|
Adverse Events
Low Dose Acetaminophen
Serious events: 0 serious events
Other events: 21 other events
Deaths: 0 deaths
High Dose Acetaminophen
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Placebo
Serious events: 2 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Low Dose Acetaminophen
n=61 participants at risk
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=67 participants at risk
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=69 participants at risk
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Apnea
|
0.00%
0/61 • 24 hours
|
1.5%
1/67 • 24 hours
|
0.00%
0/69 • 24 hours
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/61 • 24 hours
|
0.00%
0/67 • 24 hours
|
1.4%
1/69 • 24 hours
|
|
Blood and lymphatic system disorders
Leucocytosis
|
0.00%
0/61 • 24 hours
|
0.00%
0/67 • 24 hours
|
1.4%
1/69 • 24 hours
|
Other adverse events
| Measure |
Low Dose Acetaminophen
n=61 participants at risk
Participants receive a low dose of acetaminophen for 24 hours
|
High Dose Acetaminophen
n=67 participants at risk
Participants receive a high dose of acetaminophen for 24 hours
|
Placebo
n=69 participants at risk
Participants receive matching placebo for 24 hours
|
|---|---|---|---|
|
Cardiac disorders
Tachycardia
|
0.00%
0/61 • 24 hours
|
0.00%
0/67 • 24 hours
|
8.7%
6/69 • 24 hours
|
|
Gastrointestinal disorders
Vomiting
|
11.5%
7/61 • 24 hours
|
3.0%
2/67 • 24 hours
|
5.8%
4/69 • 24 hours
|
|
Gastrointestinal disorders
Constipation
|
4.9%
3/61 • 24 hours
|
3.0%
2/67 • 24 hours
|
2.9%
2/69 • 24 hours
|
|
General disorders
Pyrexia
|
4.9%
3/61 • 24 hours
|
4.5%
3/67 • 24 hours
|
18.8%
13/69 • 24 hours
|
|
Investigations
Body temperature increased
|
4.9%
3/61 • 24 hours
|
0.00%
0/67 • 24 hours
|
0.00%
0/69 • 24 hours
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
4.9%
3/61 • 24 hours
|
4.5%
3/67 • 24 hours
|
1.4%
1/69 • 24 hours
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
8.2%
5/61 • 24 hours
|
0.00%
0/67 • 24 hours
|
4.3%
3/69 • 24 hours
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Disclosure of individual investigator/site results is restricted for 18 months after final evaluation of study results or after release of a cooperative publication including all study from all sites, whichever occurs first. The sponsor has 60 days to review and comment on the publication and can request removal of any confidential information prior to public disclosure or publication.
- Publication restrictions are in place
Restriction type: OTHER