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

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ClinicalTrials.gov Identifier: NCT01768637
Recruitment Status : Completed
First Posted : January 15, 2013
Results First Posted : April 19, 2019
Last Update Posted : April 19, 2019
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
University of Texas Southwestern Medical Center

Tracking Information
First Submitted Date  ICMJE January 10, 2013
First Posted Date  ICMJE January 15, 2013
Results First Submitted Date  ICMJE March 28, 2018
Results First Posted Date  ICMJE April 19, 2019
Last Update Posted Date April 19, 2019
Actual Study Start Date  ICMJE January 2013
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid [ Time Frame: 2 weeks ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: January 11, 2013)
Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid [ Time Frame: 2 weeks ]
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.
Change History Complete list of historical versions of study NCT01768637 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 16, 2019)
  • Whole Blood Platelet Aggregation to 2 µg/mL Collagen [ Time Frame: 2 weeks ]
    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
  • Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate [ Time Frame: 4 weeks ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: January 11, 2013)
  • von Willebrand factor (vWF) activity [ Time Frame: baseline ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: January 11, 2013)
Cytochrome P450 monoxygenase system polymorphism [ Time Frame: 2 weeks ]
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.
 
Descriptive Information
Brief Title  ICMJE Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin Study
Official Title  ICMJE Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin
Brief 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Kidney Disease
Intervention  ICMJE
  • Drug: Aspirin
    Aspirin 81 mg by mouth daily
    Other Name: ASA
  • Drug: Clopidogrel
    Clopidogrel 75 mg by mouth once daily
    Other Name: Plavix
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Aspirin
    • Drug: Clopidogrel
  • 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.
    Interventions:
    • Drug: Aspirin
    • Drug: Clopidogrel
Publications * Jain N, Li X, Adams-Huet B, Sarode R, Toto RD, Banerjee S, Hedayati SS. Differences in Whole Blood Platelet Aggregation at Baseline and in Response to Aspirin and Aspirin Plus Clopidogrel in Patients With Versus Without Chronic Kidney Disease. Am J Cardiol. 2016 Feb 15;117(4):656-663. doi: 10.1016/j.amjcard.2015.11.029. Epub 2015 Dec 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 16, 2019)
48
Original Estimated Enrollment  ICMJE
 (submitted: January 11, 2013)
36
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date April 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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,
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01768637
Other Study ID Numbers  ICMJE 12CRP11830004
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: we will upload informed consent form and the study protocol.
Supporting Materials: Study Protocol
Supporting Materials: Informed Consent Form (ICF)
Time Frame: upon completion of the study and the publication
Access Criteria: everyone
Responsible Party University of Texas Southwestern Medical Center
Study Sponsor  ICMJE University of Texas Southwestern Medical Center
Collaborators  ICMJE American Heart Association
Investigators  ICMJE
Principal Investigator: Susan Hedayati, MD University of Texas Southwestern Medical Center
PRS Account University of Texas Southwestern Medical Center
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP