Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin Study
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic
Study type: Interventional
Phase: Phase 1

Summary: 
      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: 
      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.
    

Intervention name(s): Aspirin; Clopidogrel
Intervention type(s): Drug; Drug
Intervention description(s): Aspirin 81 mg by mouth daily; Clopidogrel 75 mg by mouth once daily
Other intervention name(s): ASA; Plavix
Intervention MeSH terms: Aspirin; Clopidogrel
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Chronic kidney disease; Platelet function; aspirin; antiplatelet agent