Trial Outcomes & Findings for Safety of Intravenous Acetaminophen Vs Placebo for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males (NCT NCT00493311)
NCT ID: NCT00493311
Last Updated: 2016-10-19
Results Overview
The primary efficacy endpoint was WSTD6 defined as the weighted sum of temperature differences from the temperature at each assessment timepoint through 6 hours compared with the temperature at T0, weighted by the time elapsed between each 2 consecutive timepoints.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
60 participants
Primary outcome timeframe
Baseline (T0) to 6 hours post study drug administration
Results posted on
2016-10-19
Participant Flow
Subjects were recruited at a single clinical research facility in the United States during July to September 2007.
Eligible subjects received intravenous endotoxin to induce fever and were then randomized to receive either 1 g acetaminophen in 100 ml intravenous solution or 100 ml placebo solution.
Participant milestones
| Measure |
Intravenous (IV) Placebo
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
Overall Study
STARTED
|
29
|
31
|
|
Overall Study
COMPLETED
|
27
|
29
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
| Measure |
Intravenous (IV) Placebo
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
Overall Study
Need for rescue medication
|
2
|
2
|
Baseline Characteristics
Safety of Intravenous Acetaminophen Vs Placebo for the Treatment of Endotoxin-Induced Fever in Healthy Adult Males
Baseline characteristics by cohort
| Measure |
Intravenous (IV) Placebo
n=29 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
n=31 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
30.0 years
STANDARD_DEVIATION 10.02 • n=5 Participants
|
29.7 years
STANDARD_DEVIATION 7.35 • n=7 Participants
|
29.9 years
STANDARD_DEVIATION 8.67 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=5 Participants
|
31 Participants
n=7 Participants
|
60 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=5 Participants
|
31 participants
n=7 Participants
|
60 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (T0) to 6 hours post study drug administrationThe primary efficacy endpoint was WSTD6 defined as the weighted sum of temperature differences from the temperature at each assessment timepoint through 6 hours compared with the temperature at T0, weighted by the time elapsed between each 2 consecutive timepoints.
Outcome measures
| Measure |
Intravenous (IV) Placebo
n=29 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
n=31 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
Weighted Sum of Temperature Differences Over 6 Hours (WSTD6) Assessment of the Antipyretic Effect Over 6 h of a Single Dose of IV APAP vs. Placebo for Treatment of Endotoxin-induced Fever
|
-0.7 Degrees Celsius
Standard Deviation 3.32
|
-3.7 Degrees Celsius
Standard Deviation 3.58
|
SECONDARY outcome
Timeframe: Baseline (T0) to 3 hoursWSTD3 is defined as the weighted sum of temperature differences from the temperature at each assessment timepoint through the first 3 hours compared with the temperature at T0, weighted by the time elapsed between each 2 consecutive timepoints.
Outcome measures
| Measure |
Intravenous (IV) Placebo
n=29 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
n=31 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
Weighted Sum of Temperature Differences Over 3 Hours (WSTD3) Assessment of the Antipyretic Effect Over 3 Hours of a Single Dose of IV APAP vs. Placebo for Treatment of Endotoxin-induced Fever.
|
0.7 Degrees Celsius
Standard Deviation 1.36
|
-0.9 Degrees Celsius
Standard Deviation 1.35
|
SECONDARY outcome
Timeframe: Baseline (T0) to 360 minutes (6 hours) post study drug administrationOutcome measures
| Measure |
Intravenous (IV) Placebo
n=29 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
n=31 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
Maximum Temperature Change During the Period From T0 to T360 Minutes (6 Hours After Study Drug Administration)
|
-0.9 Degrees celsius
Standard Deviation 0.75
|
-1.3 Degrees celsius
Standard Deviation 0.65
|
SECONDARY outcome
Timeframe: 360 minutes (6 hours after study drug administration)Outcome measures
| Measure |
Intravenous (IV) Placebo
n=29 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
n=31 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
The Percentage of Subjects With Temperature Less Than 38 Degrees Celsius at Any Timepoint During the Time From T0 to T360 Minutes (6 Hours After Study Drug Administration)
|
3 Percentage of participants
|
13 Percentage of participants
|
SECONDARY outcome
Timeframe: Baseline (T0) to 6 hoursSubject Global Evaluation was assessed by subject using a 4 point categorical scale in response to the following question:Overall, how would you rate the study treatments? 0 = Poor 1. = Fair 2. = Good 3. = Excellent
Outcome measures
| Measure |
Intravenous (IV) Placebo
n=29 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
n=31 Participants
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
Global Assessment of Treatment at T360 Minutes or Early Termination.
Rate treatment as 'poor'
|
2 participants
|
1 participants
|
|
Global Assessment of Treatment at T360 Minutes or Early Termination.
Rate treatment as 'fair'
|
9 participants
|
5 participants
|
|
Global Assessment of Treatment at T360 Minutes or Early Termination.
Rate treatment as 'good'
|
10 participants
|
16 participants
|
|
Global Assessment of Treatment at T360 Minutes or Early Termination.
Rate treatment as 'excellent'
|
8 participants
|
9 participants
|
Adverse Events
Intravenous (IV) Placebo
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Intravenous (IV) Acetaminophen 1 g
Serious events: 0 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Intravenous (IV) Placebo
n=29 participants at risk
After induction of fever by endotoxin administration, subjects received one infusion of 100 ml intravenous placebo solution
|
Intravenous (IV) Acetaminophen 1 g
n=31 participants at risk
After induction of fever by endotoxin administration, subjects received one infusion of 1 g of acetaminophen in 100 ml intravenous solution
|
|---|---|---|
|
Investigations
Alanine aminotransferase increased
|
20.7%
6/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
16.1%
5/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Investigations
Aspartate aminotransferase increased
|
13.8%
4/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
19.4%
6/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Investigations
Blood bilirubin increased
|
3.4%
1/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
9.7%
3/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.3%
3/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
3.2%
1/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Nervous system disorders
Dizziness
|
6.9%
2/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
6.5%
2/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Investigations
Gamma-glutamyltransferase increased
|
27.6%
8/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
16.1%
5/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
General disorders
Mucosal dryness
|
6.9%
2/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
3.2%
1/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Gastrointestinal disorders
Nausea
|
13.8%
4/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
6.5%
2/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Gastrointestinal disorders
Vomiting
|
10.3%
3/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
3.2%
1/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Metabolism and nutrition disorders
Dehydration
|
6.9%
2/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
3.2%
1/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Nervous system disorders
Headache
|
10.3%
3/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
0.00%
0/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
|
Nervous system disorders
Somnolence
|
6.9%
2/29 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
0.00%
0/31 • Treatment Emergent Adverse Events(TEAEs)were reported from T0 (on or after the start of study medication) to 6 hours after study medication was administered to the subject.
TEAEs are adverse events that start on or after the study medication is given to the subject.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Investigator may publish only after cooperative publication or 18 months after sponsor's final evaluation of study data, whichever occurs first. At least 60 days prior to submission for publication, investigator must submit manuscript to sponsor for review and comment. Sponsor has 60 day period thereafter to respond with comment. Investigator will remove confidential information at the request of sponsor.
- Publication restrictions are in place
Restriction type: OTHER