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

NCT01768637 | Completed Phase 1 Results

• 1 other identifier: 12CRP11830004
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Kidney Disease

Keywords

Chronic kidney disease; Platelet function; aspirin; antiplatelet agent

Outcome Measures

Primary Outcomes (1)

• Whole Blood Platelet Aggregation to 0.5 Millimoles Arachidonic Acid

  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

  2 weeks

Secondary Outcomes (2)

• Whole Blood Platelet Aggregation to 2 µg/mL Collagen

  2 weeks

• Whole Blood Platelet Aggregation to 20 µg/mL Adenosine Diphosphate

  4 weeks

Study Arms (2)

Chronic Kidney Disease

EXPERIMENTAL

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; Drug: Clopidogrel

Normal controls

ACTIVE COMPARATOR

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; Drug: Clopidogrel

Interventions

Aspirin DRUG

Aspirin 81 mg by mouth daily

Also known as: ASA

Chronic Kidney Disease; Normal controls

Clopidogrel DRUG

Clopidogrel 75 mg by mouth once daily

Also known as: Plavix

Chronic Kidney Disease; Normal controls

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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,

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• American Heart Association: collaborator

Study Sites (1)

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8856, United States

Location

Related Publications (2)

• 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.

  PMID: 26725101 RESULT

• 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.

  PMID: 31664940 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

Aspirin; Clopidogrel

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

Limited by residual confounding due to small sample size and lack of randomization ex vivo measurement of platelet function which may be different from in vivo function Sub-optimal reproducibility of platelet assays

Results Point of Contact

• Title: Nishank Jain, MD
• Organization: University of Arkansas for Medical Sciences

njain2@uams.edu

5016865295

Study Officials

• Susan Hedayati, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2013
• First Posted: January 15, 2013
• Study Start: January 1, 2013
• Primary Completion: April 1, 2014
• Study Completion: June 1, 2014
• Last Updated: April 19, 2019
• Results First Posted: April 19, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: upon completion of the study and the publication
• Access Criteria: everyone

Locations

US (1)