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

Sponsor

Hôpital Charles Foix (Other)

Overall Status

Completed

CT.gov ID

NCT02464488

Collaborator

University of Paris 5 - Rene Descartes (Other), Sorbonne University (Other), Assistance Publique - Hôpitaux de Paris (Other)

232

Enrollment

Locations

79.8

Actual Duration (Months)

116

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	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 Design

Study Type:

Observational

Actual Enrollment :

232 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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.

Actual Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

May 30, 2021

Actual Study Completion Date :

Aug 25, 2021

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

Pharmacologic parameters of new oral anticoagulants in elderly patients [1 to 3 weeks]
Estimated area under the curve (AUC) of each of the 3 drugs studied

Secondary Outcome Measures

Thromboembolic events [1 year]
Any thromboembolic event (composite of ischemic stroke, systemic embolism or acute coronary syndrome) in the year after inclusion
Hemorrhagic events [1 year]
Major hemorrhagic events in the year after inclusion

Eligibility Criteria

Criteria

Ages Eligible for Study:

80 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hôpital Charles Foix	Ivry-sur-Seine	Île-de-France	France	94205
2	Hôpital Européen Georges Pompidou	Paris	Île-de-France	France	75015

Sponsors and Collaborators

Hôpital Charles Foix
University of Paris 5 - Rene Descartes
Sorbonne University
Assistance Publique - Hôpitaux de Paris

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