Chronic Kidney Disease (CKD) Platelet Study

NCT03649711 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: 2279971241997
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 2

Brief Summary

This study evaluates how aspirin, clopidogrel and ticagrelor work in people with chronic kidney disease (CKD) compared to people with normal kidneys. In the first part of the study, half of CKD participants will be randomly assigned to ticagrelor and aspirin, while the other half will be assigned to clopidogrel and aspirin in a blinded fashion. The treatment duration will be two weeks. After recruiting CKD participants the investigator will recruit controls with normal kidney function that will receive only ticagrelor and aspirin for two weeks.

Conditions

Chronic Kidney Diseases; Heart Attack; Stroke, Ischemic

Keywords

P2Y12 inhibitors; Platelet aggregation; ticagrelor; clopidogrel; chronic kidney disease

Outcome Measures

Primary Outcomes (1)

• ADP Induced Platelet Aggregation

  We will use summary statistics to describe the distribution of the data. Post-treatment ADP-induced WBPA value in ohms (Ω) will be the primary outcome variable. We will use an analysis of covariance (ANCOVA) model to compare the treatment effects of ticagrelor vs. clopidogrel in CKD patients because this approach has higher statistical power than other methods to analyze drug effects. T

  2 weeks

Secondary Outcomes (1)

• Platelet Surface P-selectin Expression

  2 weeks

Study Arms (3)

CKD-Ticagrelor

EXPERIMENTAL

Ticagrelor 90 mg twice daily (double blind, random assignment) + aspirin 81 mg/d

Drug: Ticagrelor 90mg; Drug: Aspirin 81 mg

CKD-Clopidogrel

ACTIVE COMPARATOR

Clopidogrel 75 mg/day in the morning and a matching placebo in the evening to conceal frequency (double blind, random assignment) + aspirin 81 mg/d

Drug: Clopidogrel 75mg; Drug: Aspirin 81 mg

Control-ticagrelor

ACTIVE COMPARATOR

Open label ticagrelor, 90 mg twice daily + aspirin 81 mg/d

Drug: Ticagrelor 90mg; Drug: Aspirin 81 mg

Interventions

Ticagrelor 90mg DRUG

Ticagrelor Pill

Also known as: Brilinta

CKD-Ticagrelor; Control-ticagrelor

Clopidogrel 75mg DRUG

Clopidogrel Pill and a matching placebo to conceal frequency

Also known as: Plavix

CKD-Clopidogrel

Aspirin 81 mg DRUG

Aspirin Pill

Also known as: baby aspirin

CKD-Clopidogrel; CKD-Ticagrelor; Control-ticagrelor

Eligibility Criteria

• Age: 18 Years - 91 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females, aged 18-91 years
• Ability to understand and sign informed consent after the nature of the study has been fully explained
• CKD participants: Non-dialysis CKD patients: Presence of CKD with an estimated GFR of \<30 mL/min/1.73 m2 for a period of ≥3 months, as defined by the National Kidney Foundation (NKF) and determined with the CKD-EPI creatinine-based formula
• Controls with normal kidney function: participants with an estimated GFR \>90 mL/min/1.73 m2 as determined by the CKD-EPI creatinine-based formula and a urine albumin-to-creatinine ratio \<30 mg/g as defined by the National Kidney Foundation

You may not qualify if:

• No healthcare power of attorney to sign informed consent
• Unwillingness or inability to participate in the protocol or comply with any of its components.
• Subjects unable or unwilling to stop taking:
• Aspirin and other antithrombotic agents, like cilostazol, ranolazine, aggrenox, prasugrel, warfarin, xarelto, pradaxa, eliquis.
• Glycoprotein IIb/IIIa antagonist (abciximab-ReoPro, eptifibatide-Integrilin, tirofiban-Aggrastal)
• NSAIDs and PPIs
• Fish oil, Vitamin E and herbal supplements
• Acute kidney injury superimposed on CKD
• Kidney transplant or any other solid organ transplant recipient
• End-stage kidney disease on maintenance dialysis (peritoneal or hemodialysis)
• Nephrotic syndrome defined as nephrotic range proteinuria, hypoalbuminemia, hyperlipidemia and generalized edema
• Recent hospitalization or surgery \<3 months
• Acute coronary or cerebrovascular event in the last 12 months
• Blood dyscrasias, active bleeding, or bleeding diathesis
• Gastrointestinal bleeding in the last 6 months

Sponsors & Collaborators

• University of Arkansas: lead
• American Society of Nephrology: collaborator

Study Sites (2)

Central Arkansas Veterans Affairs Hospital

Little Rock, Arkansas, 72205, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (2)

• Jain N, Corken A, Arthur JM, Ware J, Arulprakash N, Dai J, Phadnis MA, Davis O, Rahmatallah Y, Mehta JL, Hedayati SS, Smyth S. Ticagrelor inhibits platelet aggregation and reduces inflammatory burden more than clopidogrel in patients with stages 4 or 5 chronic kidney disease. Vascul Pharmacol. 2023 Feb;148:107143. doi: 10.1016/j.vph.2023.107143. Epub 2023 Jan 20.

  PMID: 36682595 DERIVED

• Natale P, Palmer SC, Saglimbene VM, Ruospo M, Razavian M, Craig JC, Jardine MJ, Webster AC, Strippoli GF. Antiplatelet agents for chronic kidney disease. Cochrane Database Syst Rev. 2022 Feb 28;2(2):CD008834. doi: 10.1002/14651858.CD008834.pub4.

  PMID: 35224730 DERIVED

Related Links

• publication

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Myocardial Infarction; Ischemic Stroke

Interventions

Ticagrelor; Clopidogrel; Aspirin

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; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Necrosis; Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Dr. Nishank Jain, Associate Professor of Medicine
• Organization: University of Arkansas for Medical Sciences

njain2@uams.edu

5016865295

Study Officials

• Jain Nishank, MD

  University of Arkansas for Medical

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: CKD participants will be randomly assigned into one of the 2 study groups: ticagrelor (90 mg) one pill in the morning and one pill in the evening, or, clopidogrel (75 mg) one pill in the morning + placebo one pill in the evening. Placebo looks like the study drug but has no medicine in it. Neither participant nor the study personnel will know about allocation. The study drugs will look the same, except aspirin pill which will be dispensed to everyone in an open label manner. There is no masking for control with normal kidney function. Participants will be asked to take open label ticagrelor, 90 mg twice daily (one pill in the morning and one pill in the evening) and aspirin 81 mg/day.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: CKD participants will be double-blind randomized in these two arms: Arm 1 - Ticagrelor, 90 mg twice daily (one pill in the morning and one pill in the evening) + Aspirin 81 mg/day. Ticagrelor is the test treatment. Arm 2 - Clopidogrel, 75 mg/day in the morning and a matching placebo in the evening + Aspirin 81 mg/day. Clopidogrel is the reference treatment. Arm 3: Control with normal kidney function will be recruited after matching for age and diabetes status to the Arm 1 participants. Participants will be asked to take Ticagrelor, 90 mg twice daily (one pill in the morning and one pill in the evening) and aspirin 81 mg/day. Open label treatment. All participants are required to take the oral treatment for a total of two weeks.

Study Record Dates

• First Submitted: August 21, 2018
• First Posted: August 28, 2018
• Study Start: November 1, 2018
• Primary Completion: September 2, 2021
• Study Completion: September 2, 2021
• Last Updated: December 29, 2022
• Results First Posted: December 29, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 2 years after study closure indefinitely

Locations

US (2)