Clinical trial NCT01768637: Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin Study
Official title: Whole Blood Platelet Aggregation in Chronic Kidney Disease Patients on Aspirin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Kidney Disease
Keywords: Chronic kidney disease
Platelet function
aspirin
antiplatelet agent
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: American Heart Association
First posted: 2013-01-15
Enrollment: 48
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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,

Primary outcomes:
measure: Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid
timeFrame: 2 weeks
Secondary outcomes:
measure: Whole Blood Platelet Aggregation to 2 µg/mL Collagen
timeFrame: 2 weeks
measure: Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Susan Hedayati, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Jain N, Wan F, Kothari M, Adelodun A, Ware J, Sarode R, Hedayati SS. Association of platelet function with depression and its treatment with sertraline in patients with chronic kidney disease: analysis of a randomized trial. BMC Nephrol. 2019 Oct 29;20(1):395. doi: 10.1186/s12882-019-1576-7.