A Genomic Approach to Warfarin Dose Prescription in Admixed Caribbean Hispanics

NCT02345356 | Completed

• 2 other identifiers: A40702158G12MD007600
• Study Type: observational
• Target: 200
• Locations: 2 countries
• Sites: 3

Brief Summary

Caribbean Hispanics are a population with a disproportionately high prevalence of cardio-metabolic disorders but with a limited expectation of benefits from current pharmacogenetic algorithms derived mainly in subjects of relatively pure ancestry. The investigators focus on warfarin responses to develop urgently-needed DNA-driven prescription guidelines for this population, who have arisen from European, West African and Amerindian genomic origins to produce a highly heterogeneous population. Our project combines admixture analysis and DNA-sequencing with development of more accurate rules for better predictability of warfarin dosing to immediately serve this medically underserved population.

Conditions

Atrial Fibrillation; Deep Vein Thrombosis; Cardiac Valvular Insufficiency; Coagulopathies; Pulmonary Embolism

Keywords

Pharmacogenomics; Warfarin; Caribbean Hispanics; Polymorphisms; Dosing Algorithm

Outcome Measures

Primary Outcomes (1)

• time spent within therapeutic range

  percentage of time each patient spent within and out of the therapeutic range (TTR) during initiation, using the Rosendaal linear interpolation method.

  6 months

Secondary Outcomes (3)

• number of warfarin dose adjustments

  12 weeks

• time to stable anticoagulation

  12 weeks

• events-free time

  6 months

Study Arms (2)

Standard-of-Care

the standard clinical approach will be followed

Other: Standard-of-Care

Genotype-guided

algorithmically guided personalized therapy of warfarin, using a pharmacogenetic model developed in Caribbean Hispanics

Genetic: Genotype-guided

Interventions

Genotype-guided GENETIC

Individual warfarin dose adjustments by using a pharmacogenetically driven algorithm

Genotype-guided

Standard-of-Care OTHER

Individual warfarin dose adjustments by using a clinically driven algorithm (standard care)

Standard-of-Care

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Caribbean Hispanics (e.g., Puerto Ricans, Dominicans, Cubans), whose parents are Caribbean Hispanics as well.

You may qualify if:

• Caribbean Hispanic origin (e.g., Puerto Ricans, Dominicans, Cubans), whose parents are Caribbean Hispanics as well
• Age ≥ 21 years and ≤90 years.
• Willingness and ability to sign informed consent.
• Able to be followed up over 3 months.
• Expected duration of warfarin therapy of at least 3 months.
• Anticoagulation management for the patient will be performed in-hospital and/or as an outpatient by clinicians (i.e., participating Physicians, PharmD) that will adhere to the study dosing algorithms and dose-titration plans.

You may not qualify if:

• Non-Hispanic patients (race/ethnicity is self-reported by the patients)
• Age \<21 years and \>90 years.
• Currently taking warfarin or any other new oral anticoagulant (e.g., Xarelto, Pradaxa, Eliquis, and Savaysa/Lixiana).
• Prior warfarin therapy with known required stable dose.
• Clinician opinion that warfarin dosing needs to be adjusted for reasons not accounted for by dosing algorithm (i.e., other than age, gender, body size, co-meds, comorbidities, diet, genetics, ancestry, INRs and target INR).
• Abnormal baseline INR (off warfarin), e.g., due to liver disease, antiphospholipid antibody
• Contraindication to warfarin treatment for at least 3 months.
• Life expectancy of less than 1 year.
• Pregnant women or childbearing women not using medically approved method of birth control.
• Inability to follow-up on a regular basis with anticoagulation practitioners participating in trial.
• Any factors likely to limit adherence to warfarin, (e.g., dementia, alcohol or substance abuse, plans to move in the next 3 months, history of unreliability in medication taking or appointment keeping, significant concerns about participation in the study from spouse, significant other, or family members, lack of support from primary health care provider).
• Sickle cell, HIV-positive/ AIDS patients
• Cognitive or other causes of inability to provide informed consent or follow study procedures.
• Participating in another trial that prohibits participation in the current trial or planned enrollment in such a trial within the first 3 months of warfarin therapy.
• Anemia: a reduction in Hg ≥2g/dl within 48 hours before randomization and requiring blood transfusions.

Sponsors & Collaborators

• University of Puerto Rico: lead
• National Institute on Minority Health and Health Disparities (NIMHD): collaborator
• Genomas, Inc: collaborator

Study Sites (3)

Miami VA Healthcare System

Miami, Florida, 33125, United States

Location

UPR University Hospital at Carolina

Carolina, 00984, Puerto Rico

Location

UDH University Hospital at Centro Medico

San Juan, 00936, Puerto Rico

Location

Related Publications (5)

• Claudio-Campos K, Duconge J, Cadilla CL, Ruano G. Pharmacogenetics of drug-metabolizing enzymes in US Hispanics. Drug Metab Pers Ther. 2015 Jun;30(2):87-105. doi: 10.1515/dmdi-2014-0023.

  PMID: 25431893 BACKGROUND

• Claudio-Campos K, Orengo-Mercado C, Renta JY, Peguero M, Garcia R, Hernandez G, Corey S, Cadilla CL, Duconge J. Pharmacogenetics of healthy volunteers in Puerto Rico. Drug Metab Pers Ther. 2015 Dec;30(4):239-49. doi: 10.1515/dmpt-2015-0021.

  PMID: 26501165 BACKGROUND

• Duconge J, Cadilla CL, Seip RL, Ruano G. Why admixture matters in genetically-guided therapy: missed targets in the COAG and EU-PACT trials. P R Health Sci J. 2015 Sep;34(3):175-7. No abstract available.

  PMID: 26454897 BACKGROUND

• Duconge J, Ramos AS, Claudio-Campos K, Rivera-Miranda G, Bermudez-Bosch L, Renta JY, Cadilla CL, Cruz I, Feliu JF, Vergara C, Ruano G. A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics. PLoS One. 2016 Jan 8;11(1):e0145480. doi: 10.1371/journal.pone.0145480. eCollection 2016.

  PMID: 26745506 BACKGROUND

• Claudio-Campos K, Labastida A, Ramos A, Gaedigk A, Renta-Torres J, Padilla D, Rivera-Miranda G, Scott SA, Ruano G, Cadilla CL, Duconge-Soler J. Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study. Front Pharmacol. 2017 Jun 7;8:347. doi: 10.3389/fphar.2017.00347. eCollection 2017.

  PMID: 28638342 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Buccal swabs

MeSH Terms

Conditions

Atrial Fibrillation; Venous Thrombosis; Hemostatic Disorders; Pulmonary Embolism

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Jorge Duconge, PhD

  University of Puerto Rico Medical Sciences Campus

  PRINCIPAL INVESTIGATOR

• Graciela M. Vega-Debien, BSc

  University of Puerto Rico Medical Sciences Campus

  STUDY DIRECTOR

• Angel Lopez-Candales, MD

  University of Puerto Rico Medical Sciences Campus

  STUDY DIRECTOR

• Alga S. Ramos, PharmD

  Miami VA Hospital

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD, MSc, BSc Pharm, Professor

Study Record Dates

• First Submitted: January 19, 2015
• First Posted: January 26, 2015
• Study Start: January 1, 2016
• Primary Completion: May 17, 2022
• Study Completion: May 17, 2022
• Last Updated: May 19, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share

Locations

PR (2); US (1)