Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin Study

Study Overview
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Brief Summary
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Higher coronary in-stent thromboses and bleeding complications on anti-platelet agents are more common in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Poor inhibition of platelet aggregation by anti-platelet agents predicts future cardiovascular events. Clinical practice guidelines are ambiguous about the use of these agents in Chronic Kidney Disease due to lack of controlled studies. The investigators hypothesize that patients with Chronic Kidney Disease compared with non-Chronic Kidney Disease have reduced platelet aggregation and poor platelet inhibitory response to aspirin. The aims are to 1) define the range of whole blood platelet aggregation in stages 3-5 Chronic Kidney Disease patients; 2) investigate whether patients with stages 4-5 Chronic Kidney Disease vs. non-Chronic Kidney Disease have lower platelet aggregation or impaired von Willebrand Factor activity; and 3) compare inhibition of platelet aggregation from baseline after 2 weeks of aspirin therapy and another 2 weeks of clopidogrel therapy added to aspirin in Chronic Kidney Disease vs. non-Chronic Kidney Disease patients. Accomplishing these aims will provide pilot data to power future studies of targeted anti-platelet agent treatments in Chronic Kidney Disease in order to improve cardiovascular outcomes.

Detailed Description
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Patients will be consented for the study and asked to initial on the consent form to state whether they agree for the genetic testing. After signing informed consent, complete medical history and medication list will be obtained and verified with the electronic medical record. After meeting all inclusion and exclusion criteria during the screening visit, those patients on aspirin for primary prevention of cardiovascular events will be asked to stop it for 2 weeks prior to blood collection for baseline data. Normal controls will be chosen after frequency matching for decade of age, gender, diabetes mellitus and interval of body mass index (5 kg/m2). Dietary supplements (Vitamin E and fish oil) known to affect platelet function will be assessed and patients on those will be asked to discontinue these. Participants with also be asked to not eat foods known to affect platelet function (coffee, chocolate, grapes, and alcohol) 48 hours prior to sample collection on visit 1. An interviewer-administered assessment of diet and exercise with a modified 24-hour dietary recall and the Stanford 7-day Physical activity Recall will be performed to ensure dietary consistency which may affect platelet aggregability on visit 1. Blood will be drawn via venopuncture for laboratory studies (whole blood platelet aggregation, von Willebrand Factor antigen levels and activity). Participants will be administered aspirin 81 mg for 2 weeks and asked to return in 2 weeks. On visit 2, whole blood platelet aggregation will be re-measured and questionnaires filled out. Two oral swabs will be taken from those participants who consented for genetic testing and samples will be stored at Dallas Veterans Affairs Medical Center for short term until shipped to Diagnostics Laboratory for genetic testing of clopidogrel cytochrome P450 polymorphisms. All participants will be administered clopidogrel 75 mg daily on top of aspirin 81 mg for 2 weeks and asked to return in 2 weeks. On visit 3, whole blood platelet aggregation will be re-measured and questionnaires filled out. At the completion of the study, participants will be placed back on their original antiplatelet agent if applicable and referred back to the primary care provider.

Official Title
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Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Drug: Aspirin
* Drug: Clopidogrel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >21 years Cases: Chronic kidney disease stages 4-5, with estimated glomerular filtration rate of <30 Controls: estimated glomerular filtration rate of >90, urinary albumin to creatinine ratio <30 and no other kidney damage Exclusion Criteria: End-stage renal disease (peritoneal dialysis and hemodialysis) Kidney transplant or any other transplant patient Recent hospitalizations <3 months Acute coronary or cerebrovascular event in the last 12 months Surgery in the last 3 months Blood dyscrasias or active bleeding Gastro-intestinal bleeding in the last 6 months Concomitant use of other anti-platelet agent or antithrombotic drugs Recent treatment (<30 days) with a glycoprotein antagonist or proton pump inhibitor Hematocrit <25% or white blood cell count >20,000 or platelet count <50,000 Any active malignancy or liver disease No current diagnosis of depression, not on any antidepressant medications,

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chronic Kidney Disease<br>Patients with pre-dialysis stages 4-5 Chronic Kidney Disease will receive open-label aspirin 81 mg once daily for 2 weeks, then 2 weeks of aspirin 81 mg plus clopidogrel 75 mg once daily. | Drug: Aspirin<br>* Aspirin 81 mg by mouth daily<br>* Other names: ASA;Drug: Clopidogrel<br>* Clopidogrel 75 mg by mouth once daily<br>* Other names: Plavix;|
| Active Comparator: Normal controls<br>Patients without Chronic Kidney Disease will receive open-label aspirin 81 mg once daily for 2 weeks, then 2 weeks of aspirin 81 mg plus clopidogrel 75 mg once daily. | Drug: Aspirin<br>* Aspirin 81 mg by mouth daily<br>* Other names: ASA;Drug: Clopidogrel<br>* Clopidogrel 75 mg by mouth once daily<br>* Other names: Plavix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid | Citrated whole blood was used to measure platelet aggregation induced by agonist (arachidonic acid at 5 mM concentration) using impedance whole blood platelet aggregometry via a Chrono-log aggregometer. Values at baseline (visit 1) was compared between groups with post treatment values (visit 2) after 2 weeks of aspirin treatment | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Whole Blood Platelet Aggregation to 2 µg/mL Collagen | Citrated whole blood was used to measure platelet aggregation induced by agonist (collagen at 2mM concentration) using impedance whole blood platelet aggregometry via a Chrono-log aggregometer. Values at baseline (visit 1) was compared between groups with post treatment values (visit 2) after 2 weeks of aspirin treatment | 2 weeks | 
| Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate | Citrated whole blood was used to measure platelet aggregation induced by agonist (adenosine diphosphate at 20mM concentration) using impedance whole blood platelet aggregometry via a Chrono-log aggregometer. Values at baseline (visit 1) and on aspirin (visit 2) was compared between groups with post treatment values (visit 3) after 2 weeks of aspirin and clopidogrel treatment | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic kidney disease, Platelet function, aspirin, antiplatelet agent