Predictive Factors for Response to New Oral Anticoagulants in the Treatment of Non-valvular Atrial Fibrillation..

Identification of Clinical and Pharmacogenetic Factors Predictive of Response to New Oral Anticoagulants in the Treatment of Non-valvular Atrial Fibrillation.

Post-authorization observational, prospective, follow-up study of a cohort of patients with non-valvular atrial fibrillation who are treated with direct oral anticoagulants (DOACs) to evaluate the clinical course (occurrence of stroke, major bleeding and mortality) and its correlation with clinical, pharmacokinetic (plasma concentrations), pharmacodynamic (haemostatic) and pharmacogenetic factors.

Study Overview

• Status: Active, not recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Drug: Apixaban; Drug: Edoxaban; Drug: Rivaroxaban; Drug: Dabigatran

Detailed Description

Post-authorization observational, prospective, follow-up study of a cohort of patients with non-valvular atrial fibrillation treated with direct oral anticoagulants (dabigatran, rivaroxaban, apixaban and edoxaban) to assess the clinical course (occurrence of stroke, other ischemic or bleeding events and mortality) and its correlation with clinical, pharmacokinetic (plasma concentrations), pharmacodynamic (haemostatic) and pharmacogenetic factors.

Patient selection and follow-up will be performed in 6 public Spanish hospitals: Hospital Universitario de la Princesa, Hospital Universitario La Paz, Hospital Universitario Ramón y Cajal, Fundación Jiménez Díaz, Hospital Gómez Ulla (Madrid) and Hospital Universitario de Burgos (Burgos). To reduce variability, the determination of anticoagulant activity will be performed in the Hematology Service of the Hospital Universitario de Burgos and the measurement of plasma concentrations and genotyping of all patients in the Clinical Pharmacology Service of the Hospital Universitario de la Princesa.

Patients who are to receive or are receiving one of the four DOACs currently available in Spain will be informed about the characteristics of this study and will be asked to sign the consent form for their participation. The treatment or clinical management of these patients at each centre will not be modified. They will be asked three blood samples, coinciding with other tests that will be carried out to monitor their pathology (one blood sample for the study of the effect on coagulation, another for drug quantification in plasma and another for genetic studies) with the only requirement that they must have been treated with the drug for at least one week so that they have spent more than 5 half-lives and are in steady state. The samples will be extracted in the morning, before medication intake (trough concentrations).

• Study Type: Observational
• Enrollment (Estimated): 700

Contacts and Locations

Study Locations

• Spain
  • Burgos, Spain, 09006
    • Hospital Universitario de Burgos
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28046
    • Hospital Universitario de La Paz
  • Madrid, Spain, 28028
    • Hospital Gómez Ulla
  • Madrid, Spain, 28040
    • Hospital Universitario Fundación Jiménez Díaz:

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Men and women over 18 years of age with NVAF requiring anticoagulant treatment with a DOAC. The prescription of the treatment will be previous and independent to the inclusion of the patient in the study. Patients who will initiate treatment (which will only be evaluated prospectively) and patients already in treatment (which will also be evaluated retrospectively) will be included.

Description

Inclusion Criteria:

1. Men or women over 18 years of age
2. Patients with non-valvular atrial fibrillation (NVAF).
3. Patients who are going to receive or are receiving treatment with any of the DOACs (dabigatran, rivaroxaban, apixaban or edoxaban) for the prevention of stroke and systemic embolism in adult patients with NVAF, according to the drug label.
4. Patients who agree to participate in the study and give their written consent.

Exclusion Criteria:

1. Patients on treatment with other anticoagulants.
2. Patients suffering from a malignant or terminal disease whose life expectancy is less than 6 months.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients that satisfy inclusion criteria; Patients who satisfy the inclusion criteria and sign the informed consent.	Drug: Apixaban; Drug indicated for the treatment of NVAF; Other Names: Eliquis; Drug: Edoxaban; Drug indicated for the treatment of NVAF; Other Names: Lixiana; Drug: Rivaroxaban; Drug indicated for the treatment of NVAF; Other Names: Xarelto; Drug: Dabigatran; Drug indicated for the treatment of NVAF; Other Names: Pradaxa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major haemorrhages	Occurrence of haemorrhages will be monitored throughout the follow-up, i.e. for at least 15 months and up to 30.	Throughout the follow-up, i.e. for at least 15 months and up to 30.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemorragic stroke	Occurrence of haemorragic stroke will be monitored throughout the follow-up i.e. for at least 15 months and up to 30..	Throughout the follow-up, i.e. for at least 15 months and up to 30.
Ischemic stroke	Occurrence of ischemic stroke will be monitored throughout the follow-up i.e. for at least 15 months and up to 30..	Throughout the follow-up, i.e. for at least 15 months and up to 30.
Death	All-cause mortality will be monitored throughout the follow-up i.e. for at least 15 months and up to 30..	Throughout the follow-up, i.e. for at least 15 months and up to 30.

Collaborators and Investigators

• Sponsor: Fundación de Investigación Biomédica - Hospital Universitario de La Princesa

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2020
• Primary Completion (Estimated): September 30, 2023
• Study Completion (Estimated): September 30, 2023

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: March 3, 2020
• First Posted (Actual): March 5, 2020

Study Record Updates

• Last Update Posted (Actual): June 6, 2023
• Last Update Submitted That Met QC Criteria: June 5, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban; Dabigatran; Apixaban; Edoxaban
• Other Study ID Numbers: SFC-NAC-2019-01

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No