The Effects of Dexmedetomidine and Propofol on Cerebral B... | NCT01200433

The Effects of Dexmedetomidine and Propofol on Cerebral B... | NCT01200433 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
propofol	Active Comparator	Subjects will be sedated with propofol.	Drug: propofol
dexmedetomidine	Active Comparator	Subjects will be sedated with dexmedetomidine.	Drug: dexmedetomidine

Interventions

Name	Type	Description	Arm Group Labels	Other Names
dexmedetomidine	Drug	Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cerebral Blood Flow	Cerebral blood flow was the average of right and left carotid velocities recorded by transcranial Doppler.	For patients randomized to dexmedetomidine: at the first peak of study drug (i.e., at peak dose of study drug during first infusion period); for patients randomized to propofol: when infusion of propofol stopped.
Brain Oxygen	Brain oxygenation values were estimated by near-infrared spectroscopy and brain oxygenation was averaged across the first and second study drug infusion periods.	during first (10-20 minutes) and second (throughout the procedure) study drug infusion periods

Secondary Outcomes

Measure	Description	Time Frame
Cerebral Blood Flow	The investigator will test the hypothesis that dexmedetomidine is non-inferior to propofol for cerebral blood flow as measured by transcranial Doppler and brain oxygenation as measured by near-infrared spectroscopy.	after procedure, in post anesthesia care unit (PACU)
Alertness/Sedation

Contacts/Locations Module

Name	Affiliation	Role
Ehab Farag, MD	The Cleveland Clinic	Principal Investigator

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

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28891839	Derived	Farag E, Kot M, Podolyak A, Argalious M, Deogaonkar M, Mascha EJ, Xu Z, Katzan I, Ebrahim Z. The relative effects of dexmedetomidine and propofol on cerebral blood flow velocity and regional brain oxygenation: A randomised noninferiority trial. Eur J Anaesthesiol. 2017 Nov;34(11):732-739. doi: 10.1097/EJA.0000000000000662.

Arm/Group Information

ID	Title	Description
FG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
FG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00123 subjects
COMPLETED		FG00021 subjects FG00123 subjects
NOT COMPLETED		FG0000 subjects FG0010 subjects

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
BG001	Dexmedetomidine

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

Cerebral Blood Flow

Cerebral blood flow was the average of right and left carotid velocities recorded by transcranial Doppler.

Posted

Median

Inter-Quartile Range

cm/sec

For patients randomized to dexmedetomidine: at the first peak of study drug (i.e., at peak dose of study drug during first infusion period); for patients randomized to propofol: when infusion of propofol stopped.

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

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	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Ehab Farag, MD	Clevland Clinic Foundation	216-444-9950		farage@ccf.org

Intervention Browse Module

ID	Term
D020927	Dexmedetomidine
D015742	Propofol

ID	Term
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds

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		t-test, 1 sided		0.011		Ratio of Geometric Means	0.94			2-Sided	90	0.84	1.05			Dexmedetomidine vs. propofol	Yes	Non-Inferiority or Equivalence	We tested a joint hypothesis that dexmedetomidine was noninferior to propofol both in terms of cerebral blood flow velocity and brain oxygenation during DBS surgery. A total of 44 patients provided a 90% power at the 0.05 significance level to detect noninferiority of dexmedetomidine to propofol using a noninferiority ratio of geometric means of 0.80, assuming a coefficient of variation of 25% for each of the 2 primary outcomes. Both outcomes were expected to follow a log-normal distribution.

Primary

Brain Oxygen

Brain oxygenation values were estimated by near-infrared spectroscopy and brain oxygenation was averaged across the first and second study drug infusion periods.

Posted

Median

Inter-Quartile Range

% oxygenation

during first (10-20 minutes) and second (throughout the procedure) study drug infusion periods

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Units	Counts
Participants	OG00021 OG00123

Title

Denominators

Categories

Title	Measurements
	OG00073.5(70.3 to 76.6) OG00172.7(70.0 to 75.3)

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		t-test, 1 sided		< 0.001		Ratio of Geometric Means	0.99			2-Sided	90	0.96	1.02			Dexmedetomidine vs. propofol	Yes	Non-Inferiority or Equivalence	We tested a joint hypothesis that dexmedetomidine was noninferior to propofol both in terms of cerebral blood flow velocity and brain oxygenation during DBS surgery. A total of 44 patients provided a 90% power at the 0.05 significance level to detect noninferiority of dexmedetomidine to propofol using a noninferiority ratio of geometric means of 0.80, assuming a coefficient of variation of 25% for each of the 2 primary outcomes. Both outcomes were expected to follow a log-normal distribution.

Secondary

Cerebral Blood Flow

The investigator will test the hypothesis that dexmedetomidine is non-inferior to propofol for cerebral blood flow as measured by transcranial Doppler and brain oxygenation as measured by near-infrared spectroscopy.

The cerebral flow at PACU was not planned as a primary outcome. The primary outcome was cerebral flow at the first peak of study drug. The data was collect for information purpose only. No test was done for cerebral blood flow at PACU.

Posted

Mean

Standard Deviation

cm/sec

after procedure, in post anesthesia care unit (PACU)

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Units	Counts
Participants	OG00021 OG00123

Title

Denominators

Categories

Title	Measurements
	OG00055± 18.1 OG00146.7± 10.5

Secondary

Alertness/Sedation

Modified observer's assessment of alertness /sedation (OAA/S) scale which ranges from 0 to 5 (0 = does not respond to noxious stimuli and 5 = responds to name spoken in normal tone)

Posted

Median

Inter-Quartile Range

units on a scale

at the first peak during DBS surgery

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Units	Counts
Participants	OG00021 OG00123

Title

Denominators

Categories

Title	Measurements
	OG0002(1 to 2) OG0013(2 to 3)

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		Wilcoxon (Mann-Whitney)		<0.001		Median Difference (Final Values)	1			2-Sided	99	0	2				No	Superiority or Other

Secondary

Pulsatility Index

Pulsatility index is a measure of the variability of blood velocity in a vessel, and was calculated as the difference between the peak systolic and minimum diastolic velocities divided by the mean velocity during the cardiac cycle.

Posted

Median

Inter-Quartile Range

units on a scale

at the first peak during DBS surgery

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Units	Counts
Participants	OG00021 OG00123

Title

Denominators

Categories

Title	Measurements
	OG0001(0.89 to 1.05) OG0011(0.92 to 1.15)

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		Wilcoxon (Mann-Whitney)		0.91		Ratio of Geometric Means	1			2-Sided	99	0.86	1.18				No	Superiority or Other

Secondary

Cerebral Perfusion Pressure

Posted

Median

Inter-Quartile Range

mmHg

at the first peak during DBS surgery

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Units	Counts
Participants	OG00021 OG00123

Title

Denominators

Categories

Title	Measurements
	OG00053.9(45.1 to 69.8) OG00154.6(48.9 to 66.0)

Secondary

Number of Hypertensive Episodes

The number of hypertensive episodes during Deep Brain Stimulation (DBS) surgery.

Posted

Mean

Standard Deviation

number of episodes

During DBS surgery

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Units	Counts
Participants	OG00021 OG00123

Title

Denominators

Categories

Title	Measurements
	OG0004.9± 2.7 OG0012.9± 2.5

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		Wilcoxon (Mann-Whitney)		0.02		Median Difference (Final Values)	-1.9			2-Sided	99	-4.1	0.2				No	Superiority or Other

Secondary

Number of Apneic Episodes.

The number of antihypertensive interventions during Deep Brain Stimulation (DBS) surgery.

Posted

Median

Inter-Quartile Range

number of episodes

during DBS surgery

ID	Title	Description
OG000	Propofol	Subjects will be sedated with propofol. propofol: Patients assigned to propofol will be given an infusion dose of 50-75 µ/kg/min which will be titrated to the patient's response
OG001	Dexmedetomidine	Subjects will be sedated with dexmedetomidine. dexmedetomidine: Patients assigned to dexmedetomidine will be given a mg/kg bolus over 10-20 minutes; subsequently, an infusion will be titrated to between 0.4-0.6 mcg/kg/hr to maintain an adequate level of sedation during the procedure.

Units	Counts
Participants	OG00021 OG00123

Title

Denominators

Categories

Title	Measurements
	OG0000(0 to 0) OG0010(0 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		Wilcoxon (Mann-Whitney)		>0.99		Median Difference (Final Values)	0			2-Sided	99	0	0				No	Superiority or Other