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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University of Texas Southwestern Medical Center
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01768637
First received: January 10, 2013
Last updated: January 11, 2013
Last verified: January 2013
  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

Resource links provided by NLM:


Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01768637

Contacts
Contact: Nishank Jain, MD 214-645-8290 nishank.jain@va.gov
Contact: Kyle West 214-645-8290 Kyle.West@UTSouthwestern.edu

Locations
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         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
American Heart Association
Investigators
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
Renal Insufficiency
Urologic Diseases
Aspirin
Clopidogrel
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Sensory System Agents

ClinicalTrials.gov processed this record on November 27, 2014