New Oral Direct Anticoagulants in Patients 80 Years Old and Over : a Population Pharmacokinetics Study (ADAGE)

Study of Interindividual Variability in the Response to New Oral Direct Anticoagulants (Dabigatran Etexilate, Rivaroxaban or Apixaban) in Patients 80 Years Old and Over, Using a Population Pharmacokinetics Approach.

Several new oral direct anticoagulants have been recently marketed. However, only a few, limited, studies have provided data about the pharmacology of new oral direct anticoagulants in older persons. This study try to better define wether the pharmacology of each of these 3 drugs (dabigatran, rivaroxaban and apixaban) is actually significantly different in very older patients (over 80) and to which extend. The investigators also try to characterize the main determinants (age, weight, renal function, co-morbidities, etc) of the variability observed between individuals in their response to he drugs studied. The method employed is a population pharmacokinetic/pharmacodynamic study.

Study Overview

• Status: Completed
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Other: Plasma drug concentrations

Detailed Description

Several new oral direct anticoagulants have been recently marketed. A main indication for taking these drugs is atrial fibrillation and, in everyday practice, most patients with atrial fibrillation are older people. However, only a few, limited, studies have provided data about the pharmacology of new oral direct anticoagulants in older persons. Furthermore, this limited data strongly suggests that, in older patients, mean concentrations, overall exposition and half-live of these drugs are increased, as compared with younger people. This study try to better define wether the pharmacology of each of these 3 drugs (dabigatran, rivaroxaban and apixaban) is actually significantly different in very older patients (over 80) and to which extend. The investigators also try to characterize the main determinants (age, weight, renal function, co-morbidities, etc) of the variability observed between individuals in their response to he drugs studied. The method employed is a population pharmacokinetic/pharmacodynamic study. This is, many people (projected 225 patients) will have a few blood samples each and all data will be pooled using statistical methods specific to this kind of studies. Each patient will have one to five blood samples, taken at te same time that routine blood analysis, to determine plasma concentrations of the studied drug. In addition, patients will be followed for thrombotic and haemorrhagic events at 6 and 12 months.

• Study Type: Observational
• Enrollment (Actual): 232

Contacts and Locations

Study Locations

• France
  • Île-de-France
    • Ivry-sur-Seine, Île-de-France, France, 94205
      • Hôpital Charles Foix
    • Paris, Île-de-France, France, 75015
      • Hôpital Europeen Georges Pompidou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 80 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients aged 80 years or older under treatment with dabigatran, rivaroxaban or apixaban because atrial fibrillation

Description

Inclusion Criteria:

• Age 80 years or older
• Under treatment with dabigatran, rivaroxaban or apixaban
• For non-valvular atrial fibrillation

Exclusion Criteria:

• Mechanical (non-biological) heart valve
• Any severe condition leading to a short estimated life expectance (a few months)

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Main cohort (only cohort of the study); Patients aged 80 years or older under treatment with dabigatran, rivaroxaban or apixaban because atrial fibrillation. All patients will have plasma drug concentrations measured and will be followed afterwards similarly	Other: Plasma drug concentrations; Measure of plasma concentrations of the anticoagulant drug taken by the patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacologic parameters of new oral anticoagulants in elderly patients	Estimated area under the curve (AUC) of each of the 3 drugs studied	1 to 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thromboembolic events	Any thromboembolic event (composite of ischemic stroke, systemic embolism or acute coronary syndrome) in the year after inclusion	1 year
Hemorrhagic events	Major hemorrhagic events in the year after inclusion	1 year

Collaborators and Investigators

• Sponsor: Hôpital Charles Foix
• Collaborators: Assistance Publique - Hôpitaux de Paris; University of Paris 5 - Rene Descartes; Sorbonne University
• Investigators: Principal Investigator: Carmelo Lafuente, MD, PhD, Hôpital Charles Foix, APHP, Université Paris 6 UPMC; Principal Investigator: Julien Le Guen, MD, Hôpital Européen Georges Pompidou, APHP, Université Paris 5 Descartes

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2015
• Primary Completion (Actual): May 30, 2021
• Study Completion (Actual): August 25, 2021

Study Registration Dates

• First Submitted: June 2, 2015
• First Submitted That Met QC Criteria: June 3, 2015
• First Posted (Estimate): June 8, 2015

Study Record Updates

• Last Update Posted (Actual): August 27, 2021
• Last Update Submitted That Met QC Criteria: August 26, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Anticoagulants; Factor Xa Inhibitors; Antithrombins; Aged, 80 years and older
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation
• Other Study ID Numbers: cfx-adage-2015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO