Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin Study (WiCKDonASA)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Chronic Kidney Disease |
Drug: Aspirin Drug: Clopidogrel |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin |
- Whole Blood Platelet Aggregation to 0.5 millimoles arachidonic acid [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Compare the inhibition of Whole Blood Platelet Aggregation to 0.5 millimoles once daily of aspirin in patients with pre-dialysis stages 4-5 Chronic Kidney Disease vs. those with normal renal function. These labs will be repeated and compared between groups also after 2 weeks addition of 75 mg daily of clopidogrel to aspirin.
- von Willebrand factor (vWF) activity [ Time Frame: baseline ] [ Designated as safety issue: No ]Determine whether patients with pre-dialysis stages 4-5 chronic kidney disease, as compared to those with normal renal function, have impaired vWF activity.
- Whole Blood Platelet Aggregation to 2 µg/mL collagen [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Compare the inhibition of Whole Blood Platelet Aggregation to 2 µg/mL collagen from baseline after treatment for 2 weeks with 81 mg of aspirin daily in patients with pre-dialysis stages 4-5 Chronic Kidney Disease vs. those with normal renal function. These labs will be repeated and compared between groups also after 2 weeks addition of 75 mg daily of clopidogrel to aspirin.
- Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Compare the inhibition of Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate from baseline after treatment for 2 weeks with 81 mg of aspirin in patients with pre-dialysis stages 4-5 Chronic Kidney Disease vs. those with normal renal function. These labs will be repeated and compared between groups also after 2 weeks addition of 75 mg daily of clopidogrel to aspirin.
- beta-thromboglobulin [ Time Frame: baseline ] [ Designated as safety issue: No ]Determine whether patients with pre-dialysis stages 4-5 chronic kidney disease, as compared to those with normal renal function, have different platelet function as measured by beta-thromboglobulin.
- Platelet factor 4 [ Time Frame: baseline ] [ Designated as safety issue: No ]Determine whether patients with pre-dialysis stages 4-5 chronic kidney disease, as compared to those with normal renal function, have different platelet function as measured by platelet factor 4.
- Cytochrome P450 monoxygenase system polymorphism [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]Proportion of patients with cytochrome P450 monoxygenase system polymorphism (via oral swabs) in chronic kidney disease vs. in normal renal function patients will be measured after 2 weeks of exposure to clopidogrel at 75 mg daily plus aspirin 81 mg daily for 2 weeks.
| Estimated Enrollment: | 36 |
| Study Start Date: | January 2013 |
| Estimated Study Completion Date: | June 2014 |
| Estimated Primary Completion Date: | April 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Chronic Kidney Disease
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
Aspirin 81 mg by mouth daily
Other Name: ASA
Drug: Clopidogrel
Clopidogrel 75 mg by mouth once daily
Other Name: Plavix
|
|
Active Comparator: Normal controls
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
Aspirin 81 mg by mouth daily
Other Name: ASA
Drug: Clopidogrel
Clopidogrel 75 mg by mouth once daily
Other Name: Plavix
|
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.
Eligibility| Ages Eligible for Study: | 21 Years to 90 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
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,
Contacts and Locations| Contact: Nishank Jain, MD | 214-645-8290 | nishank.jain@va.gov |
| Contact: Kyle West | 214-645-8290 | Kyle.West@UTSouthwestern.edu |
| United States, Texas | |
| University of Texas Southwestern Medical Center | Recruiting |
| Dallas, Texas, United States, 75390-8856 | |
| Contact: Nishank Jain, MD 214-645-8290 nishank.jain@utsouthwestern.edu | |
| Principal Investigator: Susan Hedayati, MD | |
| Principal Investigator: | Susan Hedayati, MD | University of Texas Southwestern Medical Center |
More Information
No publications provided
| Responsible Party: | University of Texas Southwestern Medical Center |
| ClinicalTrials.gov Identifier: | NCT01768637 History of Changes |
| Other Study ID Numbers: | 12CRP11830004 |
| Study First Received: | January 10, 2013 |
| Last Updated: | January 11, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by University of Texas Southwestern Medical Center:
|
Chronic kidney disease Platelet function aspirin antiplatelet agent |
Additional relevant MeSH terms:
|
Kidney Diseases Renal Insufficiency, Chronic Kidney Failure, Chronic Urologic Diseases Renal Insufficiency Aspirin Clopidogrel Platelet Aggregation Inhibitors Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Pharmacologic Actions |
Anti-Inflammatory Agents Therapeutic Uses Antirheumatic Agents Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Cardiovascular Agents Hematologic Agents Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics Central Nervous System Agents Purinergic P2Y Receptor Antagonists Purinergic P2 Receptor Antagonists Purinergic Antagonists |
ClinicalTrials.gov processed this record on May 16, 2013