Pain Control After Cardiac Surgery Using Intravenous Acet... | NCT01822821

Pain Control After Cardiac Surgery Using Intravenous Acet... | NCT01822821 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
IV Acetaminophen	Experimental	Patients will receive up to four doses of IV Acetaminophen (1000mg)every six hours after surgery along with standard PCA (patient controlled) opioids.	Drug: IV Acetaminophen
Placebo	Placebo Comparator	Patients will receive up to four doses of IV placebo every six hours after surgery along with standard PCA (patient controlled) opioids.	Drug: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
IV Acetaminophen	Drug	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cumulative Opioid Consumption	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.	End of surgery through 24 hours after surgery
Pain Intensity	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).	End of surgery through 24 hours after surgery

Secondary Outcomes

Measure	Description	Time Frame
Postoperative Nausea and Vomiting	Incidence of any postoperative nausea and vomiting within 24 hours after surgery was collected.	End of surgery through 24 hours after surgery
Postoperative Sedation

Contacts/Locations Module

Name	Affiliation	Role
Negmeldeen Mamoun, MD	The Cleveland Clinic	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Cleveland Clinic		Cleveland	Ohio	44195	United States

Arm/Group Information

ID	Title	Description
FG000	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.
FG001	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.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00075 subjects FG00175 subjects
COMPLETED		FG00073 subjects FG00174 subjects
NOT COMPLETED		FG0002 subjects FG0011 subjects

Type	Comment	Reasons
Eligible surgery cancelled		FG0001 subjects FG0011 subjects
Other reasons		FG0001 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	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.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cumulative Opioid Consumption

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.

Posted

Median

Inter-Quartile Range

mg morphine equivalents

End of surgery through 24 hours after surgery

ID	Title	Description
OG000	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.
OG001	Placebo

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Nicole Zimmerman	Cleveland Clinic	216-636-9449		zimmern2@ccf.org

Condition Browse Module

ID	Term
D010146	Pain

ID	Term
D009461	Neurologic Manifestations
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms

Intervention Browse Module

ID	Term
D000082	Acetaminophen

ID	Term
D000083	Acetanilides
D000813	Anilides
D000577	Amides
D009930	Organic Chemicals
D000814

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.08		ratio of geometric means	0.89			1-Sided	90		1.06			Ratio of geometric means (CI) for IV acetaminophen versus placebo was estimated as the exponentiated treatment effect parameter from a multivariable linear regression model on log opioid consumption adjusting for age and diabetes.		Non-Inferiority or Equivalence	Noninferiority was tested using a noninferiority margin of 1.15.
OG000 OG001		Regression, Linear		0.28		ratio of geometric means	0.89			1-Sided	95		1.10			Ratio of geometric means (CI) for IV acetaminophen versus placebo was estimated as the exponentiated treatment effect parameter from a multivariable linear regression model on log opioid consumption adjusting for age and diabetes.		Superiority or Other

Primary

Pain Intensity

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).

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.

Posted

Mean

Standard Deviation

units on a scale

End of surgery through 24 hours after surgery

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

overall pain scores

- ParticipantsOG00073
- ParticipantsOG00174

Title	Measurements
	OG0003.1± 1.6

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		< 0.001		Median Difference (Final Values)	-0.9			1-Sided	90		-0.5			Difference in overall postoperative pain score means based on a repeated measures linear regression model with an autoregressive correlation structure, adjusting for age, time, and diabetes.		Non-Inferiority or Equivalence	We assessed whether IV acetaminophen is noninferior to placebo using a noninferiority margin of 1.0.

Secondary

Postoperative Nausea and Vomiting

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

Posted

Count of Participants

Participants

End of surgery through 24 hours after surgery

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

Title	Measurements
	OG00016 OG00121

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Logistic		0.35		Risk Ratio (RR)	0.76			2-Sided	99.4	0.34	1.7			Relative risk of PONV in IV acetaminophen versus placebo patients estimated from a multivariable logistic regression model using the log link and adjusting for age and diabetes.		Superiority or Other

Secondary

Postoperative Sedation

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.

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.

Posted

Median

Inter-Quartile Range

units on a scale

Measured at 8, 16, and 24 hours after surgery

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

8 hours after surgery

- ParticipantsOG00048
- ParticipantsOG00141

Title	Measurements
	OG0000(-1 to 0)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Analysis at 8 hours after surgery.	Wilcoxon (Mann-Whitney)		0.13		Median Difference (Final Values)	0			2-Sided	99.8	0	0			Difference in medians of IV acetaminophen versus placebo patients based on Wilcoxon rank sum test and Hodges-Lehmann estimation of location shift.		Superiority or Other
OG000

Secondary

Duration of Mechanical Ventilation (Minutes)

Evaluate whether IV acetaminophen reduced duration of Mechanical Ventilation.

Posted

Median

Inter-Quartile Range

minutes

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

Title	Measurements
	OG000214(143 to 345) OG001190(139 to 381)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.46		ratio of geometric means	1.3			2-Sided	99.4	0.52	3.20			Outcome log-transformed to meet model assumptions. The treatment effect on duration of mechanical ventilation was assessed by use of the ratio of geometric means from a multivariable logistic regression models adjusting for age and diabetes.		Superiority or Other

Secondary

Intensive Care Unit (ICU) Length of Stay

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

Posted

Median

Inter-Quartile Range

hours

End of surgery through discharge from ICU

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

Title	Measurements
	OG000214(143 to 345) OG001190(139 to 381)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.38		ratio of geometric means	0.93			2-Sided	99.4	0.74	1.20			Outcome log-transformed to meet model assumptions. The treatment effect on duration of ICU stay was assessed by use of the ratio of geometric means from a multivariable logistic regression models adjusting for age and diabetes.		Superiority or Other

Secondary

Hospital Length of Stay

Evaluate whether IV acetaminophen hospital length of stay

Posted

Median

Inter-Quartile Range

days

end of surgery through hospital discharge

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

Title	Measurements
	OG0006.2(5.3 to 7.3) OG0016.1(5.1 to 7.2)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.12		ratio of geometric means	1.1			2-Sided	99.4	0.94	1.20			Outcome log-transformed to meet model assumptions. The treatment effect on duration of mechanical ventilation was assessed by use of the ratio of geometric means from a multivariable logistic regression models adjusting for age and diabetes.		Superiority or Other

Secondary

Alanine Aminotransferase (ALT); U/L

Posted

Median

Inter-Quartile Range

U/L

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

Overall ALT

Title	Measurements
	OG00018(15 to 23) OG00119(15 to 24)

postoperative day 1 ALT

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.31		ratio of geometric means	1.1			2-Sided	99.4	0.9	1.2			Outcome log-transformed to meet model assumptions. The treatment effect on ALT was assessed by use of the ratio of geometric means from a repeated measures multivariable logistic regression models adjusting for age and diabetes.		Superiority or Other

Secondary

Aspartate Aminotransferase (AST); U/L

Posted

Median

Inter-Quartile Range

U/L

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

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

Overall AST

Title	Measurements
	OG00035(30 to 45) OG00133(29 to 51)

postoperative day 1 AST

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.98		ratio of geometric means	1.0			2-Sided	99.4	0.8	1.2			Outcome log-transformed to meet model assumptions. The treatment effect on AST was assessed by use of the ratio of geometric means from a repeated measures multivariable logistic regression models adjusting for age and diabetes.		Superiority or Other

Secondary

Total Bilirubin (mg/dL)

Posted

Median

Inter-Quartile Range

mg/dL

Measured at 1 day and 2 days after surgery

ID	Title	Description
OG000	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.
OG001	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.

Units	Counts
Participants	OG00073 OG00174

Title

Denominators

Categories

overall bilirubin

Title	Measurements
	OG0000.7(0.5 to 0.9) OG0010.7(0.5 to 0.8)

postoperative day 1 bilirubin

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Linear		0.40		ratio of geometric means	1.1			2-Sided	99.4	0.87	1.3			Outcome log-transformed to meet model assumptions. The treatment effect on bilirubin was assessed by use of the ratio of geometric means from a repeated measures multivariable logistic regression models adjusting for age and diabetes.		Superiority or Other