A Genomic Approach for Clopidogrel in Caribbean Hispanics

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

150 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-09-01

Study Completion Date

2024-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Clopidogrel is a prescription medicine used to minimize blood clot formation in patients with cardiovascular disease, particularly those undergoing heart catheterization and stroke. A substantial amount of medical evidence has proven that patients with stroke or heart diseases can benefit from this medicine. However, significant variability in such expected benefits has been found among individuals receiving clopidogrel, with some patients not having the benefit of reduced complications and adverse cardiovascular events. Prior studies have demonstrated a significant association between certain variants on patient's genes (e.g., CYP2C19) and poor response to clopidogrel and, therefore, major adverse cardiovascular events. Variation in other genes and other factors such as platelet activation, weight, diabetes mellitus (a medical condition that produces high blood sugar), concomitant use of other drugs, and smoking status have also been proposed to be related to the same adverse outcomes. In this study, the investigators would like to determine a possible association between these genes and the response to the medication among Caribbean Hispanic cardiovascular patients on clopidogrel. In other populations, it is known that patients with certain genetic variants have lower or magnified responses to this medication when compared to those individuals taking the same dose and not carrying the genetic variations. However, a fundamental gap remains in understanding whether the genomic diversity of Caribbean Hispanics accounts for the observed high inter-individual variability of clinical outcomes to preventive dual antiplatelet therapy (DAPT) with clopidogrel.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Implementation of CYP2C19 Genotyping to Guide Antiplatelet Therapy

NCT02724319

Coronary Artery Disease

COMPLETED

Pharmacogenetics of Clopidogrel in Acute Coronary Syndromes

NCT03347435

Acute Coronary Syndromes

TERMINATED NA

Prasugrel Versus Ticagrelor in Patients With CYP2C19 Loss-of-function: a Validation Study

NCT03489863

Coronary Artery Disease

COMPLETED PHASE4

Genotype Guided Comparison of Clopidogrel and Prasugrel Outcomes Study

NCT00995514

Cardiovascular Disease

TERMINATED

Pharmacogenomics and Effective Treatment With Clopidogrel

NCT01611545

Pharmacogenomics and Cardiovascular Events

COMPLETED

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Despite the substantial work in cardiovascular pharmacogenomics published over the past decade, a fundamental gap remains in understanding whether the genomic diversity of Caribbean Hispanics accounts for high inter-individual variability of clinical outcomes to preventive dual antiplatelet therapy (DAPT) with clopidogrel. Caribbean Hispanics are disproportionately affected by cardio-metabolic disorders, but with a limited expectation of benefits from existing genomic-based algorithms. The investigators will focus on clopidogrel to develop urgently-needed genomic-driven prescription guidelines for this population. To this purpose, the investigators will implement a treatment algorithm to guide DAPT in Caribbean Hispanics and will create a repository of genomic DNAs and fully annotated clinical and genomic datasets from Caribbean Hispanics with cardiovascular diseases. This proposal will also take a novel approach to definitively assess the admixture component and is also highly practical for the development of a clinical decision support (CDS) tool. The investigators will test the following hypothesis: There are unknown genetic variants that uniquely contribute to clopidogrel responsiveness in Caribbean Hispanics to such extent that a developed CDS tool that incorporates personal ethno-specific genotypes and ex vivo pharmacodynamics (PD) testing will help enable more precise recommendations for optimizing medical outcomes to antiplatelet therapy in this population. To test this hypothesis we will work with the following aim: To implement a treatment algorithm based on ex vivo PD and genetic test results to guide DAPT in Caribbean Hispanics.

This clinical study will be conducted over 2-3 years in 250 naive cardiovascular patients to be treated with DAPT for secondary prevention of thromboembolic events (i.e., to be compared to another set of 250 clopidogrel-treated patients from a matched non-concurrent standard-of-care cohort). It is expected that this study advances the adoption of a Precision Medicine (PM) paradigm for the benefit of Hispanic patients. The richer genetic variance in Latinos is likely to contribute substantially to variability in response to drug treatments, a component that will be missed by traditional studies within homogeneous populations. This addressable oversight is of great concern since it will tend to exacerbate the healthcare disparity already experienced by Hispanic populations in the US. Hispanics have been largely excluded from Precision Medicine initiatives, which increase dramatically the disparities in translating benefits from new findings in pharmacogenomics to this medically underserved population, exacerbating the existing inequity in healthcare services. Accordingly, the proposed research will expand the current understanding of the pharmacogenomics of Clopidogrel. Advancing knowledge in the under-investigated area of pharmacogenetics in minority populations will generate results that apply to personalize DAPT in the wider population as it moves, inevitably, toward increasing heterogeneity through admixed genomes.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cardiovascular Disease (CVD) Stroke Acute Coronary Syndrome Peripheral Arterial Disease Coronary Artery Disease Myocardial Infarction

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

After being consented, patients will undergo rapid ex vivo platelet functional testing (i.e., residual platelet reactivity units, PRU, measured using the VerifyNow P2R12 assay for Clopidogrel response) and CYP2C19 genotyping. Patients will then be categorized into 4 groups based on tests results: 1) high on-treatment platelet reactivity (HTPR)/ CYP2C19 loss-of-function (LOF) alleles (i.e., presence of both HTPR and CYP2C19 LOF alleles); 2) HTPR/No-LOF (presence of HTPR, but no CYP2C19 LOF allele); 3) No-HTPR/LOF (presence of a CYP2C19 LOF allele, but no HTPR); 4) No-HTPR/No-LOF (absence of both HTPR and CYP2C19 LOF alleles).

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

HTPR/LOF

Intervention: Genotyping (CYP2C19 assay) and P2RY12 testing to make decision on therapy.

Presence of both high on-treatment platelet reactivity (HTPR) and CYP2C19 loss-of-function (LOF) alleles:

An alternative therapy with either prasugrel or ticagrelor (in line with specific contraindications and precautions for each agent) will be strongly recommended for HPR/LOF patients, within next 5-7 days. Changes in DAPT will be at the discretion of the clinician. Treatment strategies and clinical outcomes will be evaluated up to 6-months.

Group Type EXPERIMENTAL

CYP2C19 test

Intervention Type GENETIC

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

P2RY12 assay

Intervention Type DIAGNOSTIC_TEST

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

HTPR/no-LOF

Intervention: Genotyping (CYP2C19 assay) and P2RY12 testing to make decision on therapy.

Presence of HTPR, but no CYP2C19 LOF allele found:

An alternative therapy should be considered for HTPR/no-LOF patients, within next 5-7 days. Changes in DAPT will be at the discretion of the clinician. Treatment strategies and clinical outcomes will be evaluated up to 6-months.

Group Type EXPERIMENTAL

CYP2C19 test

Intervention Type GENETIC

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

P2RY12 assay

Intervention Type DIAGNOSTIC_TEST

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

no-HTPR/LOF

Intervention: Genotyping (CYP2C19 assay) and P2RY12 testing to make decision on therapy.

Presence of a CYP2C19 LOF allele, but no HTPR:

An alternative therapy should be considered for no-HTPR/LOF patients, within next 5-7 days. Changes in DAPT will be at the discretion of the clinician. Treatment strategies and clinical outcomes will be evaluated up to 6-months.

Group Type EXPERIMENTAL

CYP2C19 test

Intervention Type GENETIC

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

P2RY12 assay

Intervention Type DIAGNOSTIC_TEST

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

No-HTPR/No-LOF

Intervention: Genotyping (CYP2C19 assay) and P2RY12 testing to make decision on therapy.

Absence of both HTPR and CYP2C19 LOF alleles:

Maintaining clopidogrel for no-HPR/no-LOF patients. Changes in DAPT will be at the discretion of the clinician. Treatment strategies and clinical outcomes will be evaluated up to 6-months.

Group Type EXPERIMENTAL

CYP2C19 test

Intervention Type GENETIC

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

P2RY12 assay

Intervention Type DIAGNOSTIC_TEST

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CYP2C19 test

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

Intervention Type GENETIC

P2RY12 assay

Patients will be categorized into 4 groups based on the results of their genetic test for CYP2C19 as well as the residual platelet reactivity test (P2RY12 assay=PRU units) and DAPT treatments options will be recommended accordingly (i.e., through a Clinical Decision Support (CDS) tool that is based on a pharmacogenetic-driven algorithm and the PRU result).

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Caribbean Hispanics (Puerto Ricans, Dominicans or Cubans) residing in Puerto Rico, whose parents are also of Hispanic origin
* Both genders (Males/Females)
* Age ≥21
* Receiving Clopidogrel for therapeutic indications.
* No clinically active hepatic abnormality
* The ability to understand the requirements of the study
* The ability to comply with study procedures and protocol
* A female patient is eligible to enter the study if she is of child-bearing potential and not pregnant or nursing, or not of child-bearing potential

Exclusion Criteria

* Non-Hispanic patients (race/ethnicity is self-reported by the patients)
* Currently enrolled in another active research protocols at the participating institutions
* BUN \>30
* Creatinine \>2.0 mg/dL
* Platelet count \<100,000/mm3
* Nasogastric or enteral feedings
* Acute illness (e.g., sepsis, infection, anemia)
* HIV/AIDS, Hepatitis B patients
* Alcoholism and drug abuse
* Patients with any cognitive and mental health impairment
* Sickle cell patients
* Active malignancy
* Patients taking another antiplatelet

Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Jorge Duconge

Proffesor, PhD

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jorge Duconge, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Puerto Rico

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University Hospital at Carolina

Carolina, , Puerto Rico

Site Status

Cardiovascular Hospital of Puerto Rico and the Caribbean

San Juan, , Puerto Rico

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Puerto Rico

References

Explore related publications, articles, or registry entries linked to this study.

Hernandez-Suarez DF, Melin K, Marin-Maldonado F, Nunez HJ, Gonzalez AF, Gonzalez-Sepulveda L, Rivas-Tumanyan S, Naik H, Ruano G, Scott SA, Duconge J. Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial. BMJ Open. 2020 Aug 6;10(8):e038936. doi: 10.1136/bmjopen-2020-038936.

Reference Type BACKGROUND

PMID: 32764090 (View on PubMed)

Duconge J, Santiago E, Hernandez-Suarez DF, Monero M, Lopez-Reyes A, Rosario M, Renta JY, Gonzalez P, Ileana Fernandez-Morales L, Antonio Velez-Figueroa L, Arce O, Marin-Maldonado F, Nunez H, Melin K, Scott SA, Ruano G. Pharmacogenomic polygenic risk score for clopidogrel responsiveness among Caribbean Hispanics: A candidate gene approach. Clin Transl Sci. 2021 Nov;14(6):2254-2266. doi: 10.1111/cts.13124. Epub 2021 Aug 20.

Reference Type RESULT

PMID: 34415683 (View on PubMed)

Nunez-Medina H, Monero M, Torres LM, Leal E, Gonzalez-Sepulveda L, Mayor AM, Renta JY, Gonzalez-Garcia ER, Gonzalez A, Melin K, Scott SA, Ruano G, Hernandez-Suarez DF, Duconge J. Implementing a Pharmacogenomic-driven Algorithm to Guide Antiplatelet Therapy among Caribbean Hispanics: A non-randomized prospective cohort study. medRxiv [Preprint]. 2023 Dec 6:2023.12.05.23299547. doi: 10.1101/2023.12.05.23299547.

Reference Type RESULT

PMID: 38106133 (View on PubMed)

Yang G, Gonzalez P, Monero M, Carrasquillo K, Renta JY, Hernandez-Suarez DF, Botton MR, Melin K, Scott SA, Ruano G, Roche-Lima A, Alarcon C, Ritchie MD, Perera MA, Duconge J. Discovery of Ancestry-specific Variants Associated with Clopidogrel Response among Caribbean Hispanics. medRxiv [Preprint]. 2023 Oct 2:2023.09.29.23296372. doi: 10.1101/2023.09.29.23296372.

Reference Type RESULT

PMID: 37873439 (View on PubMed)

Monero-Paredes M, Feliu-Maldonado R, Carrasquillo-Carrion K, Gonzalez P, Rogozin IB, Roche-Lima A, Duconge J. Non-Random Enrichment of Single-Nucleotide Polymorphisms Associated with Clopidogrel Resistance within Risk Loci Linked to the Severity of Underlying Cardiovascular Diseases: The Role of Admixture. Genes (Basel). 2023 Sep 17;14(9):1813. doi: 10.3390/genes14091813.

Reference Type RESULT

PMID: 37761953 (View on PubMed)

Nunez-Medina HJ, Monero M, Torres LM, Leal E, Gonzalez-Sepulveda L, Mayor AM, Renta JY, Gonzalez-Garcia ER, Gonzalez A, Melin K, Scott SA, Ruano G, Hernandez-Suarez DF, Duconge J. Implementing a pharmacogenomic-driven algorithm to guide antiplatelet therapy among Caribbean Hispanics: a non-randomised clinical trial. BMJ Open. 2024 Sep 5;14(9):e084119. doi: 10.1136/bmjopen-2024-084119.

Reference Type DERIVED

PMID: 39242160 (View on PubMed)

Study Documents

Access uploaded study-related documents such as protocols, statistical analysis plans, or lay summaries.

Document Type: Individual Participant Data Set

Dataset and descriptive statistics of relevant clinical and demographic data, as well as individual genotypes at several candidate genes and genetically inferred ancestry measures for the pharmacogenomic study of clopidogrel in Caribbean Hispanics.

View Document