Trial Outcomes & Findings for Safety and Efficacy of Acetaminophen in the Intensive Care Unit. (NCT NCT02280239)
NCT ID: NCT02280239
Last Updated: 2022-11-04
Results Overview
Clinically significant hypotension is defined as an acute drop in mean arterial pressure requiring treatment. Treatment is defined as either a 500 cc (or greater) fluid bolus and/or an increase in inotrope support of greater than 5 mcg/min over baseline.
TERMINATED
PHASE4
10 participants
4 hours post acetaminophen administration
2022-11-04
Participant Flow
SCREENING: Of the 950 patients who were admitted between May 28, 2015 and Jan. 20, 2016, 790 were screened, at least once. A few were screened a second time if their status had changed. ELIGIBILITY: 100 patients were eligible. RECRUITMENT: 27/100 were successfully contacted to be invited to this study. 10 consented to participate.
Of the 10 participants who were successfully recruited to the study, only 6 developed a fever while in the ICU and could be randomized into either the control or acetaminophen group
Participant milestones
| Measure |
Control Group
TOTAL: 1 Stable, febrile (temp \>38.3°C) ICU patient/participant.
Placebo: one-time dose of placebo (identical capsule) given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
Acetaminophen Group
TOTAL: 5 stable febrile (temp \>38.3°C) ICU patients/participants.
Acetaminophen: one-time dose of acetaminophen 650mg given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
|---|---|---|
|
Overall Study
STARTED
|
1
|
5
|
|
Overall Study
COMPLETED
|
1
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Safety and Efficacy of Acetaminophen in the Intensive Care Unit.
Baseline characteristics by cohort
| Measure |
Control Group
n=1 Participants
This group consists of stable but febrile ICU patients (temp \>38.3°C). Participants in this group will receive a one-time dose of placebo via the enteral route (via the gut), after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
Placebo: one-time dose of placebo (identical capsule) given via the enteral route (via the gut)
|
Acetaminophen Group
n=5 Participants
This group consists of stable but febrile ICU patients (temp \>38.3°C). Participants in this group will receive a one-time does of acetaminophen 650mg via the enteral route (via the gut), after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
Acetaminophen: one-time dose of acetaminophen 650mg given via the enteral route (via the gut)
|
Total
n=6 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
|
0 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
76 years
n=5 Participants
|
35 years
n=7 Participants
|
43.5 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
1 participants
n=5 Participants
|
5 participants
n=7 Participants
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4 hours post acetaminophen administrationClinically significant hypotension is defined as an acute drop in mean arterial pressure requiring treatment. Treatment is defined as either a 500 cc (or greater) fluid bolus and/or an increase in inotrope support of greater than 5 mcg/min over baseline.
Outcome measures
| Measure |
Control Group
n=1 Participants
TOTAL: 1 Stable, febrile (temp \>38.3°C) ICU patient/participant.
Placebo: one-time dose of placebo (identical capsule) given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
Acetaminophen Group
n=5 Participants
TOTAL: 5 stable febrile (temp \>38.3°C) ICU patients/participants.
Acetaminophen: one-time dose of acetaminophen 650mg given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
|---|---|---|
|
Clinically Significant Hypotension
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: 4 hours post interventionsystolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressures (MAP) will be monitored for 4 hours post intervention
Outcome measures
| Measure |
Control Group
n=1 Participants
TOTAL: 1 Stable, febrile (temp \>38.3°C) ICU patient/participant.
Placebo: one-time dose of placebo (identical capsule) given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
Acetaminophen Group
n=5 Participants
TOTAL: 5 stable febrile (temp \>38.3°C) ICU patients/participants.
Acetaminophen: one-time dose of acetaminophen 650mg given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
|---|---|---|
|
Blood Pressure
SBP: Pre-Intervention (2 hours)
|
141.6 mmHg
Interval 102.0 to 159.0
|
122.6 mmHg
Interval 80.0 to 170.0
|
|
Blood Pressure
SBP: Post-Intervention (4 hours)
|
141.5 mmHg
Interval 127.0 to 157.0
|
119.5 mmHg
Interval 86.0 to 158.0
|
|
Blood Pressure
DBP: Pre-Intervention (2 hours)
|
57.4 mmHg
Interval 46.0 to 63.0
|
66.2 mmHg
Interval 45.0 to 91.0
|
|
Blood Pressure
DBP: Post-Intervention (4 hours)
|
51.0 mmHg
Interval 47.0 to 55.0
|
65.4 mmHg
Interval 45.0 to 83.0
|
|
Blood Pressure
MAP: Pre-Intervention (2 hours)
|
80.8 mmHg
Interval 61.0 to 90.0
|
84.1 mmHg
Interval 56.0 to 114.0
|
|
Blood Pressure
MAP: Post-Intervention (4 hours)
|
75.5 mmHg
Interval 68.0 to 83.0
|
82.4 mmHg
Interval 61.0 to 107.0
|
SECONDARY outcome
Timeframe: 4 hours post interventionPopulation: no analysis was done because the participant in the control group received norepinephrine and only 1 participant in the acetaminophen received milrione
Total dose of all vasoactive medications will be converted to total Equidose value (with the formula 10 mcg/min norepinephrine ≈ 5 mcg/kg/min dopamine ≈ 10 mcg/min epinephrine ≈ 1 mcg/min phenylephrine ≈ 0.02 u/min vasopressin as per Russell et al. (2008)) before comparing the treatment and control groups Only 2 of the 6 participants were on low-dose vasoactive medications, (i.e., one was on norepinephrine and the other was on milrinone) therefore the pre-planned conversion calculation was not done.
Outcome measures
| Measure |
Control Group
n=1 Participants
TOTAL: 1 Stable, febrile (temp \>38.3°C) ICU patient/participant.
Placebo: one-time dose of placebo (identical capsule) given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
Acetaminophen Group
n=1 Participants
TOTAL: 5 stable febrile (temp \>38.3°C) ICU patients/participants.
Acetaminophen: one-time dose of acetaminophen 650mg given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
|---|---|---|
|
Equivalent-dose of Vasoactive Medication Post Intervention
Pre-Intervention (2 hours) TOTAL Milrinone
|
NA mcg
None given during this period
|
6000.0 mcg
|
|
Equivalent-dose of Vasoactive Medication Post Intervention
Pre-Intervention (2 hours) TOTAL Norepinephrine
|
167.0 mcg
|
NA mcg
None given during this period
|
|
Equivalent-dose of Vasoactive Medication Post Intervention
Post-Intervention (4 hours) TOTAL Norepinephrine
|
576.0 mcg
|
NA mcg
None given during this period
|
|
Equivalent-dose of Vasoactive Medication Post Intervention
Post-Intervention (4 hours) TOTAL Milrinone
|
NA mcg
None given during this period
|
7000.0 mcg
|
SECONDARY outcome
Timeframe: 4 hours post interventionTotal crystalloid and colloid fluid will be converted the the equi-volume dose (with the ratio 1.4:1 (as per Finfer et al.(2004) \& Vincent and Weil (2006) before making comparisons between the treatment and control groups.
Outcome measures
| Measure |
Control Group
n=1 Participants
TOTAL: 1 Stable, febrile (temp \>38.3°C) ICU patient/participant.
Placebo: one-time dose of placebo (identical capsule) given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
Acetaminophen Group
n=5 Participants
TOTAL: 5 stable febrile (temp \>38.3°C) ICU patients/participants.
Acetaminophen: one-time dose of acetaminophen 650mg given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
|---|---|---|
|
Equivalent-volume Fluid Administered Post Intervention
Pre-Intervention (2 hours) Total fluid INTAKE
|
235 mL
Interval 235.0 to 235.0
|
298 mL
Interval 30.0 to 736.0
|
|
Equivalent-volume Fluid Administered Post Intervention
Pre-Intervention (2 hours) Total fluid OUTPUT
|
80 mL
Interval 80.0 to 80.0
|
370 mL
Interval 140.0 to 790.0
|
|
Equivalent-volume Fluid Administered Post Intervention
Post-Intervention (4 hours) Total Fluid INTAKE
|
734 mL
Interval 734.0 to 734.0
|
612 mL
Interval 353.0 to 856.0
|
|
Equivalent-volume Fluid Administered Post Intervention
Post-Intervention (4 hours) Total Fluid OUTPUT
|
245 mL
Interval 245.0 to 245.0
|
852 mL
Interval 230.0 to 1400.0
|
SECONDARY outcome
Timeframe: 6 hours post interventionPopulation: NOTE: there was some data loss for the one participant in the control group. Temperature was recorded every 5 minutes for the first 40 minutes and then only hourly due to technical failure which may impact the accuracy of fever burden calculations.
Continuous measurements of core body temperature will be recorded for 6 hours. Fever burden (FB) is defined as area between the 6 hour temperature curve and 38.3°C cut-off and it is reported in °C-hour. PRE-INTERVENTION FB: is reported for a 2 hour period. POST-INTERVENTION FB: post-intervention fever burden is reported for a 6 hour period and average hourly fever burden. Peak Temperature: is the highest recorded temperature for the study period in °C Minimum Temperature: is the lowest recorded temperature for the study period in °C
Outcome measures
| Measure |
Control Group
n=1 Participants
TOTAL: 1 Stable, febrile (temp \>38.3°C) ICU patient/participant.
Placebo: one-time dose of placebo (identical capsule) given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
Acetaminophen Group
n=5 Participants
TOTAL: 5 stable febrile (temp \>38.3°C) ICU patients/participants.
Acetaminophen: one-time dose of acetaminophen 650mg given via the enteral route (via the gut) after which vital signs (including continuous measures of core temperature, heart rate, and blood pressure) will be monitored for 4 hours.
|
|---|---|---|
|
Fever Burden
Pre-Intervention FB (2 hours)
|
0.97 °C*hours
Interval 0.97 to 0.97
|
2.16 °C*hours
Interval 1.07 to 3.78
|
|
Fever Burden
Post-Intervention FB (6 hours)
|
0.74 °C*hours
Interval 0.74 to 0.74
|
5.65 °C*hours
Interval 1.6 to 10.24
|
Adverse Events
Control Group
Acetaminophen Group
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place