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A Multi-Center Study of the Efficacy, Pharmacokinetics (PK) and Pharmacodynamics (PD) of IV Acetaminophen for the Treatment of Acute Pain in Pediatric Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01635101
Recruitment Status : Completed
First Posted : July 6, 2012
Results First Posted : January 21, 2020
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Acute Pain
Interventions Drug: IV Acetaminophen
Drug: IV Control
Enrollment 197
Recruitment Details  
Pre-assignment Details Of 215 participants screened, 197 were actually enrolled and received study drug
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description Participants receive a low dose of acetaminophen for 24 hours Participants receive a high dose of acetaminophen for 24 hours Participants receive matching placebo administered intravenously for 24 hours
Period Title: Overall Study
Started 61 67 69
Safety Population 61 67 69
Modified Intent to Treat (mITT) 61 67 69
Pharmacokinetics Evaluable Population 50 59 58
Completed 52 55 52
Not Completed 9 12 17
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo Total
Hide Arm/Group Description Participants received a low dose of acetaminophen for 24 hours Participants receive a high dose of acetaminophen for 24 hours Participants receive matching placebo for 24 hours Total of all reporting groups
Overall Number of Baseline Participants 61 67 69 197
Hide Baseline Analysis Population Description
Modified Intent-to-Treat (mITT) population
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
All Participants Number Analyzed 61 participants 67 participants 69 participants 197 participants
Neonates (birth to ≤ 28 days)
13
  21.3%
12
  17.9%
13
  18.8%
38
  19.3%
Younger infants (≥ 29 days to < 6 mos)
16
  26.2%
20
  29.9%
18
  26.1%
54
  27.4%
Intermediate aged infants (≥ 6 mos to <12 mos)
18
  29.5%
17
  25.4%
20
  29.0%
55
  27.9%
Older infants (≥12 mos to <24 mos)
14
  23.0%
18
  26.9%
18
  26.1%
50
  25.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 67 participants 69 participants 197 participants
Female
17
  27.9%
27
  40.3%
26
  37.7%
70
  35.5%
Male
44
  72.1%
40
  59.7%
43
  62.3%
127
  64.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 61 participants 67 participants 69 participants 197 participants
American Indian or Alaska Native
1
   1.6%
0
   0.0%
0
   0.0%
1
   0.5%
Asian
3
   4.9%
4
   6.0%
6
   8.7%
13
   6.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
12
  19.7%
9
  13.4%
9
  13.0%
30
  15.2%
White
40
  65.6%
49
  73.1%
46
  66.7%
135
  68.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
5
   8.2%
5
   7.5%
8
  11.6%
18
   9.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 61 participants 67 participants 69 participants 197 participants
61 67 69 197
1.Primary Outcome
Title Total Rescue Opioid Consumption
Hide Description Total micrograms per kilogram (µg/kg) of rescue opioid used during the same 24 hours the subject is on study medication
Time Frame in 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description:
Participants receive a low dose of acetaminophen for 24 hours
Participants receive a high dose of acetaminophen for 24 hours
Participants receive matching placebo for 24 hours
Overall Number of Participants Analyzed 61 67 69
Mean (Standard Deviation)
Unit of Measure: µg/kg
166.9  (225.06) 179.9  (193.47) 180.2  (184.70)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Low Dose Acetaminophen, Placebo
Comments Difference in Least Squares (LS) Means
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.736
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -11.8
Confidence Interval (2-Sided) 97.5%
-91.0 to 67.3
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection High Dose Acetaminophen, Placebo
Comments LS Mean Difference
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.4
Confidence Interval (2-Sided) 97.5%
-75.9 to 78.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Time to First Rescue Medication
Hide Description [Not Specified]
Time Frame within 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description:
Participants receive low dose acetaminophen for 24 hours
Participants receive high dose acetaminophen for 24 hours
Participants receive placebo for 24 hours
Overall Number of Participants Analyzed 61 67 69
Median (Inter-Quartile Range)
Unit of Measure: hours
4.78
(3.15 to 16.32)
4.76
(2.15 to 10.08)
3.81
(2.25 to 8.95)
3.Secondary Outcome
Title Summary of Pain Intensity Using the Leuven Neonatal Pain Scale (LNPS) in Neonates
Hide Description The LNPS is used for assessing pain intensity in neonates. Scores on the scale run from 0-14. Higher scores mean worse pain.
Time Frame within 24 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
Neonates in the mITT population with scores at each data collection time
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description:
Participants receive low dose acetaminophen for 24 hours
Participants receive high dose acetaminophen for 24 hours
Participants receive placebo for 24 hours
Overall Number of Participants Analyzed 13 12 13
Mean (Standard Deviation)
Unit of Measure: score on a scale
at 0 hours Number Analyzed 13 participants 12 participants 13 participants
0.8  (1.09) 0.8  (1.27) 1.1  (1.26)
at 6 hours Number Analyzed 13 participants 12 participants 13 participants
1.1  (1.04) 1.0  (1.41) 1.2  (1.82)
at 12 hours Number Analyzed 13 participants 12 participants 13 participants
2.2  (1.92) 1.8  (1.76) 2.0  (1.83)
at 18 hours Number Analyzed 13 participants 12 participants 13 participants
1.0  (1.53) 1.8  (1.99) 0.8  (0.99)
at 24 hours Number Analyzed 12 participants 12 participants 13 participants
0.8  (1.40) 1.3  (1.42) 0.9  (1.40)
4.Secondary Outcome
Title Summary of Pain Intensity Using the LNPS in Younger Infants
Hide Description The LNPS is used for assessing pain intensity in younger infants. Scores on the scale run from 0-14. Higher scores mean worse pain.
Time Frame within 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Younger Infants in the mITT population with scores at each data collection time
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description:
Participants receive low dose acetaminophen for 24 hours
Participants receive high dose acetaminophen for 24 hours
Participants receive placebo for 24 hours
Overall Number of Participants Analyzed 16 20 18
Mean (Standard Deviation)
Unit of Measure: score on a scale
at 0 hours Number Analyzed 16 participants 20 participants 18 participants
2.1  (2.85) 1.5  (1.85) 2.2  (2.05)
at 6 hours Number Analyzed 16 participants 18 participants 17 participants
2.1  (2.36) 1.3  (1.33) 2.4  (3.10)
at 12 hours Number Analyzed 16 participants 18 participants 16 participants
2.2  (2.4) 1.8  (1.58) 1.9  (1.24)
at 18 hours Number Analyzed 16 participants 15 participants 14 participants
1.6  (2.25) 1.7  (2.06) 2.1  (1.44)
at 24 hours Number Analyzed 14 participants 15 participants 14 participants
2.3  (1.59) 1.3  (1.63) 2.9  (2.51)
5.Secondary Outcome
Title Pain Intensity Using the FLACC Score in Intermediate Aged Infants
Hide Description 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.
Time Frame within 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Intermediate aged infants in the mITT population with a score at each data collection time
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description:
Participants receive a low dose of acetaminophen for 24 hours
Participants receive a high dose of acetaminophen for 24 hours
Participants receive placebo for 24 hours
Overall Number of Participants Analyzed 18 17 20
Mean (Standard Deviation)
Unit of Measure: score on a scale
at 0 hours Number Analyzed 15 participants 17 participants 18 participants
0.6  (1.30) 1.6  (2.27) 1.2  (2.05)
at 6 hours Number Analyzed 14 participants 17 participants 15 participants
0.7  (0.83) 2.1  (2.71) 1.4  (2.59)
at 12 hours Number Analyzed 13 participants 17 participants 12 participants
1.2  (1.41) 0.08  (1.39) 1.8  (2.49)
at 18 hours Number Analyzed 11 participants 15 participants 13 participants
1.4  (2.01) 0.9  (1.19) 0.5  (0.97)
at 24 hours Number Analyzed 11 participants 14 participants 12 participants
1.4  (2.29) 0.9  (1.56) 0.3  (0.65)
6.Secondary Outcome
Title Pain Intensity Using the FLACC Score in Older Infants
Hide Description 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.
Time Frame within 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Older infants in the mITT population with a score at each data collection time
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description:
Participants receive a low dose of acetaminophen for 24 hours
Participants receive a high dose of acetaminophen for 24 hours
Participants receive placebo for 24 hours
Overall Number of Participants Analyzed 14 18 18
Mean (Standard Deviation)
Unit of Measure: score on a scale
at 0 hours Number Analyzed 14 participants 18 participants 17 participants
2.2  (2.64) 1.8  (2.65) 1.8  (2.37)
at 6 hours Number Analyzed 12 participants 16 participants 15 participants
0.5  (0.90) 1.2  (2.07) 1.5  (2.42)
at 12 hours Number Analyzed 12 participants 15 participants 14 participants
0.8  (1.27) 1.7  (2.76) 2.4  (1.78)
at 18 hours Number Analyzed 10 participants 14 participants 14 participants
1.3  (1.95) 0.1  (0.36) 1.3  (2.67)
at 24 hours Number Analyzed 12 participants 14 participants 12 participants
2.0  (2.59) 0.8  (1.12) 0.1  (0.29)
Time Frame 24 hours
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Low Dose Acetaminophen High Dose Acetaminophen Placebo
Hide Arm/Group Description Participants receive a low dose of acetaminophen for 24 hours Participants receive a high dose of acetaminophen for 24 hours Participants receive matching placebo for 24 hours
All-Cause Mortality
Low Dose Acetaminophen High Dose Acetaminophen Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/61 (0.00%)   0/67 (0.00%)   0/69 (0.00%) 
Hide Serious Adverse Events
Low Dose Acetaminophen High Dose Acetaminophen Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/61 (0.00%)   1/67 (1.49%)   2/69 (2.90%) 
Blood and lymphatic system disorders       
Leucocytosis  1  0/61 (0.00%)  0/67 (0.00%)  1/69 (1.45%) 
Respiratory, thoracic and mediastinal disorders       
Apnea  1  0/61 (0.00%)  1/67 (1.49%)  0/69 (0.00%) 
Hypoxia  1  0/61 (0.00%)  0/67 (0.00%)  1/69 (1.45%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Low Dose Acetaminophen High Dose Acetaminophen Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   21/61 (34.43%)   8/67 (11.94%)   24/69 (34.78%) 
Cardiac disorders       
Tachycardia  1  0/61 (0.00%)  0/67 (0.00%)  6/69 (8.70%) 
Gastrointestinal disorders       
Vomiting  1  7/61 (11.48%)  2/67 (2.99%)  4/69 (5.80%) 
Constipation  1  3/61 (4.92%)  2/67 (2.99%)  2/69 (2.90%) 
General disorders       
Pyrexia  1  3/61 (4.92%)  3/67 (4.48%)  13/69 (18.84%) 
Investigations       
Body temperature increased  1  3/61 (4.92%)  0/67 (0.00%)  0/69 (0.00%) 
Metabolism and nutrition disorders       
Hypokalaemia  1  3/61 (4.92%)  3/67 (4.48%)  1/69 (1.45%) 
Respiratory, thoracic and mediastinal disorders       
Pleural effusion  1  5/61 (8.20%)  0/67 (0.00%)  3/69 (4.35%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information Call Center
Organization: Mallinckrodt
Phone: 800-556-3314
EMail: clinicaltrials@mnk.com
Layout table for additonal information
Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT01635101    
Other Study ID Numbers: CPI-APA-353
First Submitted: June 29, 2012
First Posted: July 6, 2012
Results First Submitted: September 10, 2019
Results First Posted: January 21, 2020
Last Update Posted: January 21, 2020