Trial Outcomes & Findings for Pain Control After Cardiac Surgery Using Intravenous Acetaminophen (NCT NCT01822821)

NCT ID: NCT01822821

Last Updated: 2017-05-15

Results Overview

Evaluate the noninferiority and efficacy of IV acetaminophen; compared to a placebo, in reducing opioid consumption a after cardiac surgery. Total opioid consumption is defined as the total amount amount of opioids administered to patients converted to mg morphine equivalents.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 150 participants
• Primary outcome timeframe: End of surgery through 24 hours after surgery
• Results posted on: 2017-05-15

Participant Flow

Participant milestones

Measure	IV Acetaminophen Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Overall Study STARTED	75	75
Overall Study COMPLETED	73	74
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	IV Acetaminophen Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Overall Study Eligible surgery cancelled	1	1
Overall Study Other reasons	1	0

Baseline Characteristics

Pain Control After Cardiac Surgery Using Intravenous Acetaminophen

Baseline characteristics by cohort

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.	Total n=147 Participants Total of all reporting groups
Age, Continuous	62 years STANDARD_DEVIATION 14 • n=5 Participants	59 years STANDARD_DEVIATION 14 • n=7 Participants	60.5 years STANDARD_DEVIATION 14 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	24 Participants n=7 Participants	48 Participants n=5 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	50 Participants n=7 Participants	99 Participants n=5 Participants

PRIMARY outcome

Timeframe: End of surgery through 24 hours after surgery

Evaluate the noninferiority and efficacy of IV acetaminophen; compared to a placebo, in reducing opioid consumption a after cardiac surgery. Total opioid consumption is defined as the total amount amount of opioids administered to patients converted to mg morphine equivalents.

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Cumulative Opioid Consumption	97 mg morphine equivalents Interval 58.0 to 136.0	117 mg morphine equivalents Interval 66.0 to 174.0

PRIMARY outcome

Timeframe: End of surgery through 24 hours after surgery

Population: All patients had at least one postoperative pain scores. Some patients did not have a pain score at particular time points if they were unavailable (e.g., at a test), unable to speak (e.g., intubated), asleep, or similar reasons. We report any available pain scores at each time they were collected.

Evaluate the noninferiority and efficacy of IV acetaminophen; compared to a placebo, in reducing pain intensity scores after cardiac surgery. Pain scores were measured on the Numeric Rating scale, ranging from 0 to 10 (where 0 indicates no pain and 10 indicates the worst pain imaginable).

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Pain Intensity 24 hours after surgery	2.5 units on a scale Standard Deviation 2.1	3.5 units on a scale Standard Deviation 2.0
Pain Intensity 20 hours after surgery	2.9 units on a scale Standard Deviation 2.1	4.2 units on a scale Standard Deviation 2.0
Pain Intensity overall pain scores	3.1 units on a scale Standard Deviation 1.6	4.0 units on a scale Standard Deviation 1.4
Pain Intensity 4 hours after surgery	4.6 units on a scale Standard Deviation 2.9	5.0 units on a scale Standard Deviation 3.1
Pain Intensity 6 hours after surgery	3.5 units on a scale Standard Deviation 2.4	4.4 units on a scale Standard Deviation 2.4
Pain Intensity 8 hours after surgery	3.2 units on a scale Standard Deviation 2.6	4.4 units on a scale Standard Deviation 2.3
Pain Intensity 12 hours after surgery	2.4 units on a scale Standard Deviation 2.5	3.5 units on a scale Standard Deviation 2.6
Pain Intensity 16 hours after surgery	3.0 units on a scale Standard Deviation 2.4	3.6 units on a scale Standard Deviation 2.4

SECONDARY outcome

Timeframe: End of surgery through 24 hours after surgery

Incidence of any postoperative nausea and vomiting within 24 hours after surgery was collected.

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Postoperative Nausea and Vomiting	16 Participants	21 Participants

SECONDARY outcome

Timeframe: Measured at 8, 16, and 24 hours after surgery

Population: RASS scores were not collected at certain time points if patients were not available (e.g., patient was away at a test) or if staff were not available.

Postoperative sedation was assessed using the Richmond Agitation Sedation Scale (RASS). It ranges from -5 to +4, where -5 indicates no response to voice or physical stimulation and +4 indicates overtly combative or violent and immediate danger to staff. Lower the value, better the sedation.

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Postoperative Sedation 8 hours after surgery	0 units on a scale Interval -1.0 to 0.0	0 units on a scale Interval -1.0 to 0.0
Postoperative Sedation 16 hours after surgery	0 units on a scale Interval -1.0 to 0.0	0 units on a scale Interval 0.0 to 0.0
Postoperative Sedation 24 hours after surgery	0 units on a scale Interval 0.0 to 0.0	0 units on a scale Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: End of surgery until the initial end of ventilation or date of death from any cause, whichever came first, assessed up to 1 week.

Evaluate whether IV acetaminophen reduced duration of Mechanical Ventilation.

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Duration of Mechanical Ventilation (Minutes)	214 minutes Interval 143.0 to 345.0	190 minutes Interval 139.0 to 381.0

SECONDARY outcome

Timeframe: End of surgery through discharge from ICU

Evaluate whether IV acetaminophen reduced intensive care unit (ICU) Length of Stay.

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Intensive Care Unit (ICU) Length of Stay	214 hours Interval 143.0 to 345.0	190 hours Interval 139.0 to 381.0

SECONDARY outcome

Timeframe: end of surgery through hospital discharge

Evaluate whether IV acetaminophen hospital length of stay

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Hospital Length of Stay	6.2 days Interval 5.3 to 7.3	6.1 days Interval 5.1 to 7.2

SECONDARY outcome

Timeframe: Two days after surgery or date of death from any cause, whichever came first

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Alanine Aminotransferase (ALT); U/L Overall ALT	18 U/L Interval 15.0 to 23.0	19 U/L Interval 15.0 to 24.0
Alanine Aminotransferase (ALT); U/L postoperative day 1 ALT	18 U/L Interval 16.0 to 24.0	19 U/L Interval 15.0 to 25.0
Alanine Aminotransferase (ALT); U/L postoperative day 2 ALT	17 U/L Interval 14.0 to 22.0	18 U/L Interval 15.0 to 23.0

SECONDARY outcome

Timeframe: Two days after surgery or date of death from any cause, whichever came first

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Aspartate Aminotransferase (AST); U/L Overall AST	35 U/L Interval 30.0 to 45.0	33 U/L Interval 29.0 to 51.0
Aspartate Aminotransferase (AST); U/L postoperative day 1 AST	40 U/L Interval 32.0 to 54.0	40 U/L Interval 32.0 to 57.0
Aspartate Aminotransferase (AST); U/L postoperative day 2 AST	31 U/L Interval 24.0 to 42.0	31 U/L Interval 23.0 to 45.0

SECONDARY outcome

Timeframe: Measured at 1 day and 2 days after surgery

Outcome measures

Measure	IV Acetaminophen n=73 Participants Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids. IV Acetaminophen: Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Placebo n=74 Participants Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids. Placebo: Patients will receive up to four doses placebo every six hours after surgery along with standard PCA (patient controlled) opioids.
Total Bilirubin (mg/dL) overall bilirubin	0.7 mg/dL Interval 0.5 to 0.9	0.7 mg/dL Interval 0.5 to 0.8
Total Bilirubin (mg/dL) postoperative day 1 bilirubin	0.7 mg/dL Interval 0.5 to 1.0	0.7 mg/dL Interval 0.5 to 0.8
Total Bilirubin (mg/dL) postoperative day 2 bilirubin	0.6 mg/dL Interval 0.4 to 0.8	0.6 mg/dL Interval 0.4 to 0.8

Adverse Events

IV Acetaminophen

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

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

Nicole Zimmerman

Cleveland Clinic

Phone: 216-636-9449

Email: zimmern2@ccf.org

Results disclosure agreements

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