Aspirin Resistance and Stroke Risk: Platelet Function Analysis in Patients With Ischemic Events

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01586975
• Collaborator: (none)
• Enrollment: 93
• Location: 1
• Arms: 3
• Duration (Months): 53
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if PFA results correlate with ischemic event outcomes as well as bleeding complications. Hypothesis is antiplatelet agents will be more efficacious if they are administered in a dose-adjusted manner using PFA results as a guide.

Condition or Disease	Intervention/Treatment	Phase
Stroke; Myocardial Infarctions	Drug: Clopidogrel; Drug: Aspirin 81 mg; Drug: Aspirin >300 mg	Phase 2/Phase 3

Detailed Description

Atherothrombotic disease is a leading killer of adults throughout the world. The current mainstay for the prevention of ischemic vascular events is the use of aspirin Antiplatelet agents are used routinely for the primary and secondary prevention of vascular events in patients with a prior history of stroke, TIA, or at high risk for the development of cerebrovascular disease. Numberous individual studies and meta-analyses have shown that essentially all of the oral antiplatelet agents have limited efficacy, with relative risk reductions in the range of 20-35%. The purpose of this study is to perform serial platelet function assays (PFAs) on patients with cerebrovascular disease who are taking antiplatelet agents and perform a pilot study to determine the feasibility of administering ASA as a dose adjusted medication using PFA. The long term goal of this study is to determine whether antiplatelet therapy will be more efficacious and/or safer if it is administered in a dose-adjusted manner.

Study Design

• Study Type: Interventional
• Actual Enrollment: 93 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Multiphase Study to Determine if Platelet Function Analysis Results Correlate With Ischemic Events and Bleeding Complications
• Study Start Date: Jul 1, 2007
• Actual Primary Completion Date: Apr 1, 2010
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Clopidogrel 75 mg Clopidogrel 75 mg daily	Drug: Clopidogrel; Clopidogrel 75 mg QD; Other Names: Plavix
Active Comparator: Aspirin 81 mg open-label Aspirin 81 mg daily	Drug: Aspirin 81 mg; Aspirin 81mg QD; Other Names: Acetylsalicylic Acid ASA
Active Comparator: Aspirin > 300mg open-label Aspirin over 300 mg daily	Drug: Aspirin >300 mg; Aspirin >300 mg QD; Other Names: Acetylsalicylic Acid ASA

Outcome Measures

Primary Outcome Measures

1. PFA1 [3-6 months (Collected once between regulalary scheduled follow-up visit between 3-6 months)]

   Platelet Function Analysis (PFA) lab results: PFA was performed using the PFA 100 device (Dade-Behring), which uses a higher sheer stress flow cytometry paradigm to measure the time in seconds to closing of an aperture. Normal is defined as <172 seconds."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient must be taking Aspirin or Plavix

• Patient must have had a stroke, TIA or cerebrovascular disease

Exclusion Criteria:

-None

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Mark J Alberts, MD, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Taylor TN, Davis PH, Torner JC, Holmes J, Meyer JW, Jacobson MF. Lifetime cost of stroke in the United States. Stroke. 1996 Sep;27(9):1459-66. Review.

• Responsible Party: Northwestern University
• ClinicalTrials.gov Identifier: NCT01586975
• Other Study ID Numbers: Aspirin Resistance and Stroke; IRB#0996-007 FUND#7810
• First Posted: Apr 27, 2012
• Last Update Posted: Dec 31, 2015
• Last Verified: Dec 1, 2015

• Additional relevant MeSH terms: Stroke; Myocardial Infarction; Infarction; Aspirin; Clopidogrel

Study Results

Participant Flow

Recruitment Details	Patients with cerebrovascular disease and taking one or more antiplatelet medication were consented for study participation from 2007 though 2010. Patients were recruiting on the inpatient stroke unit at Northwestern Memorial Hospital and seen in the outpatient stroke clinic.

Arm/Group Title	Clopidogrel 75 mg	Aspirin 81 mg	Aspirin > 300 mg
Arm/Group Description	Clopidogrel 75 mg QD	Aspirin 81 mg QD	Aspiring > 300 mg QD
Period Title: Overall Study
STARTED	15	32	46
COMPLETED	15	32	46
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Clopidogrel 75 mg	Aspirin 81 mg	Aspiring >300 mg	Total
Arm/Group Description	Clopidogrel 75 mg QD	Aspirin 81 mg QD	Aspirin >300 mg QD	Total of all reporting groups
Overall Participants	15	32	46	93
Age, Customized (years) [Mean (Full Range) ]
Mean (Full Range) [years]	60.6	67.4	56.2	60.7
Sex: Female, Male (Count of Participants)
Female	9 60%	16 50%	26 56.5%	51 54.8%
Male	6 40%	16 50%	20 43.5%	42 45.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	2 6.3%	2 4.3%	4 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	2 13.3%	4 12.5%	7 15.2%	13 14%
White	13 86.7%	25 78.1%	37 80.4%	75 80.6%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 3.1%	0 0%	1 1.1%
Region of Enrollment (participants) [Number]
United States	15 100%	32 100%	46 100%	93 100%

Outcome Measures

1. Primary Outcome

Title	PFA1
Description	Platelet Function Analysis (PFA) lab results: PFA was performed using the PFA 100 device (Dade-Behring), which uses a higher sheer stress flow cytometry paradigm to measure the time in seconds to closing of an aperture. Normal is defined as <172 seconds."
Time Frame	3-6 months (Collected once between regulalary scheduled follow-up visit between 3-6 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Clopidogrel 75 mg	Aspirin 81 mg	Aspirin > 300 mg
Arm/Group Description	Clopidogrel 75 mg QD	open label Aspirin	open-label Aspirin
Measure Participants	15	32	46
Mean (Standard Error) [seconds]	202.0 (27.1)	271.1 (14.9)	234.7 (13.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Clopidogrel 75 mg, Aspirin 81 mg, Aspirin > 300 mg
	Comments	Kruskal-Wallis non-parametric ANOVA test
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0742
	Comments	p-value is not adjusted, and no a priori threshold was used
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	Patients were monitored via routine clinic/office visits to determine if they had an ischemic vascular event or hemorrhagic event. These follow-up visits were scheduled every 3-6 months as per their regularly scheduled clinic follow-up visits.
Arm/Group Title	Clopidogrel 75 mg		Aspirin 81 mg		Aspirin >300 mg
Arm/Group Description	Clopidogrel 75 mg QD		Aspirin 81 mg QD		Aspirin >300 mg QD
All Cause Mortality
	Clopidogrel 75 mg		Aspirin 81 mg		Aspirin >300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Clopidogrel 75 mg		Aspirin 81 mg		Aspirin >300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		1/32 (3.1%)		2/46 (4.3%)
Cardiac disorders
MI	0/15 (0%)	0	0/32 (0%)	0	1/46 (2.2%)	1
Vascular disorders
Clinical Stroke	0/15 (0%)	0	1/32 (3.1%)	1	0/46 (0%)	0
TIA	0/15 (0%)	0	0/32 (0%)	0	1/46 (2.2%)	1
Other (Not Including Serious) Adverse Events
	Clopidogrel 75 mg		Aspirin 81 mg		Aspirin >300 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/15 (13.3%)		3/32 (9.4%)		2/46 (4.3%)
Gastrointestinal disorders
GI bleeding	1/15 (6.7%)	1	1/32 (3.1%)	1	0/46 (0%)	0
Immune system disorders
Bruising	1/15 (6.7%)	1	0/32 (0%)	0	0/46 (0%)	0
Vascular disorders
Nose bleeds	0/15 (0%)	0	2/32 (6.3%)	2	2/46 (4.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.