Trial Outcomes & Findings for Effect of Intravenous Acetaminophen on Postoperative Opioid-related Complications (NCT NCT02156154)

NCT ID: NCT02156154

Last Updated: 2021-04-20

Results Overview

Hypoxemia is measured as minutes with hypoxemia (Spo2 \<90%) per hour of successful Spo2 monitoring. Patients will have nearly continuous pulseoximeter monitoring and recording. Data from the monitor will be downloaded daily for 48 hours postoperatively.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 580 participants
• Primary outcome timeframe: the initial 48 hours of postoperative monitoring or for the duration of hospitalization, if shorter.
• Results posted on: 2021-04-20

Participant Flow

Participant milestones

Measure	Intravenous 0.9% Sodium Chloride 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous Acetaminophen Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Overall Study STARTED	291	289
Overall Study COMPLETED	287	283
Overall Study NOT COMPLETED	4	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effect of Intravenous Acetaminophen on Postoperative Opioid-related Complications

Baseline characteristics by cohort

Measure	Intravenous 0.9% Sodium Chloride n=287 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous Acetaminophen n=283 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Total n=570 Participants Total of all reporting groups
Age, Continuous	48.4 years STANDARD_DEVIATION 15.1 • n=5 Participants	50.3 years STANDARD_DEVIATION 15.3 • n=7 Participants	49.3 years STANDARD_DEVIATION 15.2 • n=5 Participants
Sex: Female, Male Female	136 Participants n=5 Participants	140 Participants n=7 Participants	276 Participants n=5 Participants
Sex: Female, Male Male	151 Participants n=5 Participants	143 Participants n=7 Participants	294 Participants n=5 Participants
Race/Ethnicity, Customized White	265 Participants n=5 Participants	261 Participants n=7 Participants	526 Participants n=5 Participants
Race/Ethnicity, Customized Black	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	287 participants n=5 Participants	283 participants n=7 Participants	570 participants n=5 Participants
Body mass index (BMI)	26.7 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants	26.7 kg/m^2 STANDARD_DEVIATION 4.7 • n=7 Participants	26.7 kg/m^2 STANDARD_DEVIATION 4.8 • n=5 Participants

PRIMARY outcome

Timeframe: the initial 48 hours of postoperative monitoring or for the duration of hospitalization, if shorter.

Population: Patients were analyzed according to their randomized group, excluding patients who did not receive study intervention. 28 patients (5%) did not have any data recorded due to unexpected technical issues.

Hypoxemia is measured as minutes with hypoxemia (Spo2 <90%) per hour of successful Spo2 monitoring. Patients will have nearly continuous pulseoximeter monitoring and recording. Data from the monitor will be downloaded daily for 48 hours postoperatively.

Outcome measures

Measure	Intravenous Acetaminophen n=283 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=287 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Duration of Hypoxemia	0.7 min/h Interval 0.1 to 5.1	1.1 min/h Interval 0.1 to 6.6

SECONDARY outcome

Timeframe: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)

Population: Data on the outcome could not be collected for 7 patients in the IV acetaminophen group and 5 patients in the IV sodium chloride group.

Pain scores were calculated on a visual analog scale of 0 to 10, with 0 being no pain and 10 being the most pain imaginable; time weighted mean was calculated as the area under the curve of the pain score measurements divided by total measurement time. Pain was recorded at roughly 15-minute intervals in the postanesthesia care unit and at 4-hour intervals on surgical wards

Outcome measures

Measure	Intravenous Acetaminophen n=276 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=282 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Time-weighted Pain Score During Initial 48 Postoperative Hours	4.2 score on a scale Standard Deviation 1.8	4.4 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)

Population: Data on the outcome could not be collected for 2 patients in the IV acetaminophen group and 6 patients in the IV sodium chloride group.

Pain scores were calculated on a visual analog scale of 0 to 10, with 0 being no pain and 10 being the most pain imaginable; time-weighted mean was calculated as the area under the curve of the pain score measurements divided by total measurement time.

Outcome measures

Measure	Intravenous Acetaminophen n=281 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=281 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Time Weighted Pain Score in Post Anesthesia Care Unit	4.3 score on a scale Standard Deviation 1.7	4.4 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Postoperative day 1

Population: Data on the outcome could not be collected for 12 patients in the IV acetaminophen group and 15 patients in the IV sodium chloride group.

Fatigue scores were calculated on a scale of 1 to 10, with 1 being no fatigue and 10 being the worst fatigue imaginable.

Outcome measures

Measure	Intravenous Acetaminophen n=271 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=272 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Fatigue Score on Morning of Postoperative Day 1	5 score on a scale Standard Deviation 2.6	4.9 score on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)

Population: Data on the outcome could not be collected for 91 patients in the IV acetaminophen group and 86 patients in the IV sodium chloride group.

Sedation was estimated by the RASS score and recorded at 2-hour intervals by ward nurses per clinical routine during the initial 48 postoperative hours. The Richmond Agitation-Sedation Scale (RASS) is scored from -5 to +4, with -5 being unarousable, 0 being alert and calm, and +4 being combative.

Outcome measures

Measure	Intravenous Acetaminophen n=192 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=201 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Lowest RASS Score During Initial 48 Postoperative Hours	-0.96 score on a scale Standard Deviation 0.75	-0.89 score on a scale Standard Deviation 0.76

SECONDARY outcome

Timeframe: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)

Population: Data on the outcome could not be collected for 31 patients in the IV acetaminophen group and 37 patients in the IV sodium chloride group.

Treatment effect data are reported as ratios of geometric means

Outcome measures

Measure	Intravenous Acetaminophen n=252 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=248 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Time Spent in Sitting or Upright Position	2.2 hours Interval 0.8 to 4.1	2.2 hours Interval 0.9 to 4.2

SECONDARY outcome

Timeframe: Initial 48 postoperative hours

Population: Data on the outcome could not be collected for 3 patients in the IV acetaminophen group and 7 patients in the IV sodium chloride group.

Total opioid consumption over the initial 48 postoperative hours was extracted from patients' medical records and converted to intravenous morphine equivalents

Outcome measures

Measure	Intravenous Acetaminophen n=280 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=280 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Opioid Consumption - Intravenous Morphine Equivalents	50 mg Interval 18.0 to 122.0	58 mg Interval 24.0 to 151.0

SECONDARY outcome

Timeframe: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)

Population: Data on the outcome could not be collected for 3 patients in the IV acetaminophen group and 7 patients in the IV sodium chloride group.

Patients were asked about postoperative nausea and vomiting in the postanesthesia care unit, at 4-hour intervals while awake through the remaining initial day of surgery, and on the first and second postoperative mornings.

Outcome measures

Measure	Intravenous Acetaminophen n=280 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=280 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Incidence of Postoperative Nausea and Vomiting	140 Participants	124 Participants

SECONDARY outcome

Timeframe: Initial 48 postoperative hours or duration of hospitalization (whichever comes first)

Population: Data on the outcome could not be collected for 95 patients in the IV acetaminophen group and 124 patients in the IV sodium chloride group.

A low respiratory function event was defined as an episode of less than 40% of predicted minute ventilation for 2 minutes.

Outcome measures

Measure	Intravenous Acetaminophen n=188 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=163 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Incidence of Low Respiratory Function Event	52 Participants	50 Participants

SECONDARY outcome

Timeframe: Induction to extubation (3 hours on average)

Population: Data on the outcome could not be collected for 1 patient in the IV acetaminophen group.

Total anesthetic dose is measured in minimal alveolar concentration hours.

Outcome measures

Measure	Intravenous Acetaminophen n=282 Participants Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen	Intravenous 0.9% Sodium Chloride n=287 Participants 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge. Intravenous Acetaminophen
Total Anesthetic Dose From Induction to Extubation	2.9 minimal alveolar concentration hours Interval 2.6 to 3.0	2.9 minimal alveolar concentration hours Interval 2.7 to 3.0

Adverse Events

Intravenous Acetaminophen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Intravenous 0.9% Sodium Chloride

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Alparslan Turan, MD

Cleveland Clinic

Phone: 216-445-0998

Email: turana@ccf.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place