Validation of International Warfarin Pharmacogenetics Consortium (IWPC) Algorithm in Elderly Patients With Comorbidity (VIALE)

Prospective Validation of IWPC Pharmacogenetic Algorithm for Estimating the Appropriate Initial Dose of Warfarin in Elderly People (65 or Older) With Heart Valves Prostheses or Non Valvular Atrial Fibrillation and Comorbidity

The purpose of this study is to validate the International Warfarin Pharmacogenetics Consortium (IWPC) algorithm in a prospective cohort of elderly people (65 years or older) with heart valves and/or nonvalvular atrial fibrillation (AF) and at least one comorbid condition, and to assess the algorithm's prognostic relevance.

Study Overview

• Status: Unknown
• Conditions: Atrial Fibrillation; Thrombus Due to Heart Valve Prosthesis
• Intervention / Treatment: Drug: Warfarin

• Study Type: Observational
• Enrollment (Anticipated): 376

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy
    • Second University of Naples
  • Napoli, Italy
    • University of Naples Federico II
  • Salerno, Italy
    • University of Salerno

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

prospective cohort of elderly people (≥65 years) with nonvalvular atrial fibrillation and/or heart valve replacement, with at least one comorbid condition, presenting for warfarin therapy

Description

Inclusion Criteria:

• Age ≥ 65 years
• Patients who initiate warfarin because of non valvular atrial fibrillation or heart valve replacement
• At least one comorbid condition
• At least two other drugs regularly assumed over and above warfarin

Exclusion Criteria:

• Presence of systemic coagulopathies
• Presence of malignancies needing chemotherapy
• Inability or refusal to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Warfarin in elderly with comorbidity; Patients 65 years or older, candidate for therapy with warfarin for non valvular atrial fibrillation or heart valve replacement	Drug: Warfarin; warfarin treatment will be determined by treating physicians according to in-hospital guidelines, blindly to genotype assessment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients whose predicted dose of warfarin is within 20% of the actual stable therapeutic dose.	stable warfarin dosing is defined as the mean daily does required to achieve three or more consecutive International Normalized Ratio (INR) measurements within the individual's target range, at the same daily does.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients for whom the predicted dose is at least 20% higher than the actual dose (overestimation) or at least 20% lower than the actual dose (underestimation).		up to 12 months
number of cardiovascular and cerebrovascular events	composite endpoint: death for any cause, hospitalization for cardiovascular and cerebrovascular events, major bleeding or thromboembolism	12 months
number of patients with major bleeding events	major bleeding: (i) fatal bleeding; and/or (ii) symptomatic bleeding in a critical area or organ; and/or (iii) bleeding causing a fall in haemoglobin level of ≥2 g/dL or leading to transfusion of two or more units of blood or red cells.	12 months
number of thromboembolic event	thromboembolism is defined as occurrence of cerebral infarction, myocardial infarction, peripheral arterial embolism.	12 months
number of cardiovascular and cerebrovascular events		4 weeks
number of patient reported episodes of minor bleeding events		one year
average maintenance dose per patient		12 months
time to achievement of stable warfarin dosing from initiation		up to 12 months
time to therapeutic INR per patient	defined as the time of first achieving INR measurement within the individual's target range, providing that INR is also within the target range at the subsequent clinic visit	up to 12 months
percentage time in the therapeutic INR range		up to 3 months
percentage time in the therapeutic INR range		four weeks

Collaborators and Investigators

• Sponsor: University of Campania "Luigi Vanvitelli"
• Collaborators: Federico II University; University of Salerno
• Investigators: Study Chair: Ciro Gallo, MD, University of Campania "Luigi Vanvitelli"; Principal Investigator: Amelia Filippelli, MD, University of Salerno; Principal Investigator: Marisa De Feo, MD, University of Campania "Luigi Vanvitelli"; Principal Investigator: Nicola Ferrara, MD, Federico II University

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (ANTICIPATED): December 1, 2017
• Study Completion (ANTICIPATED): June 1, 2018

Study Registration Dates

• First Submitted: February 20, 2014
• First Submitted That Met QC Criteria: February 20, 2014
• First Posted (ESTIMATE): February 21, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 27, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Atrial Fibrillation; elderly; Warfarin; comorbidity; Heart Valve Prosthesis Implantation; International Warfarin Pharmacogenetics Consortium algorithm
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Anticoagulants; Warfarin
• Other Study ID Numbers: VIALE; FARM9JNT9Y (OTHER_GRANT: Agenzia Italiana per il Farmaco (AIFA)); 2012-002578-30 (EUDRACT_NUMBER)