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Safety and Efficacy of Intravenous Acetaminophen (IV APAP) in Adult Inpatients

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ClinicalTrials.gov Identifier: NCT00598559
Recruitment Status : Completed
First Posted : January 22, 2008
Results First Posted : December 10, 2010
Last Update Posted : October 21, 2016
Sponsor:
Information provided by (Responsible Party):
Mallinckrodt

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Pain
Fever
Intervention Drug: IV Acetaminophen
Enrollment 213
Recruitment Details Open label study conducted in the US from 21 Feb 2008 -12 Aug 2008
Pre-assignment Details  
Arm/Group Title IV Acetaminophen 1 Gram Every 6 Hours IV Acetaminophen 650 Milligram Every 4 Hours Standard of Care (SOC)
Hide Arm/Group Description All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours. All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours. All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them.
Period Title: Overall Study
Started 92 91 30
Completed 65 [1] 63 [1] 27 [1]
Not Completed 27 28 3
Reason Not Completed
Adverse Event             11             7             0
Withdrawal by Subject             2             2             0
Protocol Non-compliance             1             0             0
Early discharge from hospital             9             12             3
Subject unable/unwilling to attend visit             4             7             0
[1]
Subjects completed 5 days of treatment
Arm/Group Title IV Acetaminophen 1g q6h IV Acetaminophen 650 mg q4h Standard of Care (SOC) Total
Hide Arm/Group Description All Subjects Randomized to Receive IV acetaminophen 1g administered every 6 hours. All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours. All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them. Total of all reporting groups
Overall Number of Baseline Participants 92 91 30 213
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 91 participants 30 participants 213 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
48
  52.2%
54
  59.3%
17
  56.7%
119
  55.9%
>=65 years
44
  47.8%
37
  40.7%
13
  43.3%
94
  44.1%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 92 participants 91 participants 30 participants 213 participants
Female
49
  53.3%
44
  48.4%
17
  56.7%
110
  51.6%
Male
43
  46.7%
47
  51.6%
13
  43.3%
103
  48.4%
1.Primary Outcome
Title Number of Subjects Reporting at Least One Treatment-Emergent Adverse Event (TEAE).
Hide Description

Number of subjects who experienced at least one treatment emergent adverse event (TEAE).

A TEAE is an adverse event that occurs on or after the first dose of study medication (T0).

Time Frame T0 (first dose of IV APAP or randomization to SOC group) to Day 7 - 12 Follow-up
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
Arm/Group Title IV Acetaminophen 1 g q6h IV Acetaminophen 650 mg q4h Standard of Care (SOC)
Hide Arm/Group Description:
mITT Population, IV acetaminophen 1 g administered every 6 hours.
mITT Population, IV acetaminophen 650 mg administered every 4 hours.
mITT Population, Subjects Who Received Standard of Care Treatment.
Overall Number of Participants Analyzed 92 91 30
Measure Type: Number
Unit of Measure: Participants
77 86 26
2.Primary Outcome
Title Subjects Who Experienced at Least One Serious Treatment-Emergent Adverse Event (TEAE)
Hide Description

Serious TEAE is any untoward medical occurrences at any dose of study medication that:

  • results in death
  • is life threatening
  • requires inpatient hospitalization or causes prolongation of existing hospitalization
  • results in persistent or significant disability/incapacity
  • is a congenital anomaly/birth defect
  • is an important medical event
Time Frame First dose (T0) to within 30 days of the last dose of study medication.
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
Arm/Group Title IV Acetaminophen 1 g q6h IV Acetaminophen 650 mg q4h Standard of Care (SOC)
Hide Arm/Group Description:
mITT Population, IV acetaminophen 1 g administered every 6 hours.
mITT Population, IV acetaminophen 650 mg administered every 4 hours.
mITT Population, Subjects Who Received Standard of Care Treatment.
Overall Number of Participants Analyzed 92 91 30
Measure Type: Number
Unit of Measure: Participants
14 11 3
3.Secondary Outcome
Title Subject Global Evaluation of the Level of Satisfaction With Side Effects Related to Study Treatments
Hide Description Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with side effects related to study treatment at End of Day 5 (prior to discharge)
Time Frame End of Day 5 (prior to discharge)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
Arm/Group Title IV Acetaminophen 1 g q6h IV Acetaminophen 650 mg q4h Standard of Care (SOC)
Hide Arm/Group Description:
mITT Population, IV acetaminophen 1 g administered every 6 hours.
mITT Population, IV acetaminophen 650 mg administered every 4 hours.
mITT Population, Subjects Who Received Standard of Care Treatment.
Overall Number of Participants Analyzed 64 63 26
Mean (Standard Deviation)
Unit of Measure: Units on a scale
2.5  (0.78) 2.5  (0.67) 2.0  (0.85)
4.Secondary Outcome
Title Subject Global Evaluation of the Level of Satisfaction With Study Treatments Looking Back Over the Entire Treatment Period.
Hide Description Using a four point categorical scale 0= poor, 1= fair, 2= good, 3= excellent, comparisons of subject's Global Evaluations of the level of satisfaction with study treatments looking back over the entire treatment period was conducted at Day 7.
Time Frame Study period lookback at Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses were conducted using the mITT population, defined as subjects who were randomized to the IV acetaminophen groups and who received at least one dose of IV acetaminophen, and all subjects assigned to the SOC group.
Arm/Group Title IV Acetaminophen 1 g q6h IV Acetaminophen 650 mg q4h Standard of Care (SOC)
Hide Arm/Group Description:
mITT Population, IV acetaminophen 1 g administered every 6 hours.
mITT Population, IV acetaminophen 650 mg administered every 4 hours.
mITT Population, Subjects Who Received Standard of Care Treatment.
Overall Number of Participants Analyzed 81 78 26
Mean (Standard Deviation)
Unit of Measure: Units on a scale
2.4  (0.75) 2.3  (0.74) 2.2  (0.61)
Time Frame AEs were collected after the start of study medication (T0) until approximately 7 days after the last dose for IVAPAP group or 12 days from T0 for SOC group. SAEs were collected from first dose until 30 days fter the last dose
Adverse Event Reporting Description

The end of the study date was:

  • IVAPAP:7 days from the last dose of study medication or maximum assessment date, whichever was greater.
  • SOC:12 days from T0 or maximum assessment date, whichever was greater.
 
Arm/Group Title IV Acetaminophen 1 Gram Every 6 Hours IV Acetaminophen 650 Milligram Every 4 Hours Standard of Care (SOC)
Hide Arm/Group Description All Subjects Randomized to Receive IV acetaminophen 1 gram administered every 6 hours. All Subjects Randomized to Receive 650 mg IV acetaminophen administered every 4 hours. All Subjects Randomized to Receive standard of care treatment under the discretion of the Investigator and the medical staff caring for them.
All-Cause Mortality
IV Acetaminophen 1 Gram Every 6 Hours IV Acetaminophen 650 Milligram Every 4 Hours Standard of Care (SOC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
IV Acetaminophen 1 Gram Every 6 Hours IV Acetaminophen 650 Milligram Every 4 Hours Standard of Care (SOC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/92 (15.22%)   11/91 (12.09%)   3/30 (10.00%) 
Cardiac disorders       
Cardiac arrest * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Myocardial infarction * 1  1/92 (1.09%)  1/91 (1.10%)  0/30 (0.00%) 
Gastrointestinal disorders       
Gastric ulcer haemorrhage * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
Intestinal obstruction * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Oesophageal haemorrhage * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Peritonitis * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
General disorders       
Multi-organ failure * 1  1/92 (1.09%)  1/91 (1.10%)  0/30 (0.00%) 
Infections and infestations       
Abscess * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
Pelvic abscess * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Perirectal abscess * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
Pneumonia * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Postoperative wound infection * 1  2/92 (2.17%)  2/91 (2.20%)  0/30 (0.00%) 
Sepsis * 1  0/92 (0.00%)  0/91 (0.00%)  1/30 (3.33%) 
Staphylococcal infection * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Wound infection * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Injury, poisoning and procedural complications       
Gastrointestinal anastomotic leak * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Post procedural complication * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
Postoperative ileus * 1  0/92 (0.00%)  1/91 (1.10%)  1/30 (3.33%) 
Wound dehiscience * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
Investigations       
Hepatic enzyme increased * 1  0/92 (0.00%)  2/91 (2.20%)  0/30 (0.00%) 
Transaminases increased * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
Psychiatric disorders       
Mental status changes * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Renal and urinary disorders       
Renal failure acute * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Reproductive system and breast disorders       
Prostatic haemorrhage * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory failure * 1  1/92 (1.09%)  0/91 (0.00%)  0/30 (0.00%) 
Dyspnoea * 1  0/92 (0.00%)  0/91 (0.00%)  1/30 (3.33%) 
Respiratory failure * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
Vascular disorders       
Haematoma * 1  0/92 (0.00%)  1/91 (1.10%)  0/30 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IV Acetaminophen 1 Gram Every 6 Hours IV Acetaminophen 650 Milligram Every 4 Hours Standard of Care (SOC)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   60/92 (65.22%)   68/91 (74.73%)   18/30 (60.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  11/92 (11.96%)  10/91 (10.99%)  6/30 (20.00%) 
Leukocytosis * 1  3/92 (3.26%)  0/91 (0.00%)  2/30 (6.67%) 
Cardiac disorders       
Tachycardia * 1  5/92 (5.43%)  3/91 (3.30%)  1/30 (3.33%) 
Gastrointestinal disorders       
Constipation * 1  18/92 (19.57%)  21/91 (23.08%)  5/30 (16.67%) 
Nausea * 1  23/92 (25.00%)  34/91 (37.36%)  8/30 (26.67%) 
Vomiting * 1  6/92 (6.52%)  10/91 (10.99%)  1/30 (3.33%) 
Diarrhoea * 1  5/92 (5.43%)  4/91 (4.40%)  1/30 (3.33%) 
General disorders       
Oedema peripheral * 1  7/92 (7.61%)  7/91 (7.69%)  2/30 (6.67%) 
Pyrexia * 1  4/92 (4.35%)  3/91 (3.30%)  2/30 (6.67%) 
Investigations       
Breath sounds abnormal * 1  7/92 (7.61%)  6/91 (6.59%)  1/30 (3.33%) 
Metabolism and nutrition disorders       
Hypokalaemia * 1  10/92 (10.87%)  4/91 (4.40%)  2/30 (6.67%) 
Hyperglycaemia * 1  5/92 (5.43%)  2/91 (2.20%)  0/30 (0.00%) 
Hypomagnesaemia * 1  5/92 (5.43%)  2/91 (2.20%)  2/30 (6.67%) 
Nervous system disorders       
Headache * 1  7/92 (7.61%)  5/91 (5.49%)  4/30 (13.33%) 
Psychiatric disorders       
Insomnia * 1  13/92 (14.13%)  17/91 (18.68%)  5/30 (16.67%) 
Anxiety * 1  4/92 (4.35%)  2/91 (2.20%)  3/30 (10.00%) 
Skin and subcutaneous tissue disorders       
Pruritus * 1  11/92 (11.96%)  13/91 (14.29%)  2/30 (6.67%) 
Vascular disorders       
Hypertension * 1  6/92 (6.52%)  5/91 (5.49%)  0/30 (0.00%) 
Hypotension * 1  7/92 (7.61%)  9/91 (9.89%)  2/30 (6.67%) 
Phlebitis * 1  0/92 (0.00%)  1/91 (1.10%)  2/30 (6.67%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (10.0)
No separate efficacy analyses were performed for the fever because only 1 subject in each active group had fever as an indication, and no subject had both pain and fever as indications for treatment with IV acetaminophen.
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.
Before any submission is made, Cadence shall be notified of the intention to publish and shall submit the manuscript to Cadence for review and comment.At least 60 days prior to submission for publication, investigator must submit manuscript to sponsor who has 60 days for review and comment. Publication may delayed at Cadence's written request for a period not to exceed 90 days if it contains a disclosure of an invention.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Lawrence Hill
Organization: Mallinckrodt Pharmaceuticals
Phone: 908-238-6370
EMail: lawrence.hill@mallinckrodt.com
Layout table for additonal information
Responsible Party: Mallinckrodt
ClinicalTrials.gov Identifier: NCT00598559     History of Changes
Other Study ID Numbers: CPI-APA-351
First Submitted: January 8, 2008
First Posted: January 22, 2008
Results First Submitted: September 25, 2009
Results First Posted: December 10, 2010
Last Update Posted: October 21, 2016