Clinical trial NCT03854149: Apixaban in Adults With Congenital Heart Disease and Atrial Arrhythmias: the PROTECT-AR Study
Official title: A Prospective, Observational, Multicenter Study on the Safety and Efficacy of Apixaban for the Prevention of Thromboembolism in Adults With Congenital Heart Disease and Atrial Arrhythmias: the PROTECT-AR Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Heart Disease
Atrial Arrhythmia
Thromboembolism
Anticoagulants Causing Adverse Effects in Therapeutic Use
Keywords: Congenital Heart Disease
Atrial Fibrillation
Thromboembolism
NOAC
Apixaban
Atrial arrhythmias
Lead sponsor: AHEPA University Hospital
Sponsor class: OTHER
Collaborators: name: Onassis Cardiac Surgery Centre
name: Attikon Hospital
name: MITERA Children's Hospital
First posted: 2019-02-26
Enrollment: 218
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Adult patients with Congenital Heart Disease and Non-Valvular Atrial Arrhythmias who are routinely treated with apixaban (i.e., new or ongoing users) for stroke prevention at any health-care level in Greece

Brief summary: The purpose of this study is to evaluate the safety and efficacy of apixaban for the prevention of thromboembolism in adult patients with congenital heart disease (CHD) and non-valvular atrial arrhythmias (AA)

Detailed description: Adult patients with congenital heart disease (ACHD) represent a rapidly growing population due to the progress of surgical techniques and optimal medical management. Non-valvular atrial arrhythmias (AA) carries a significant burden for long-term morbidity and potentially mortality in ACHD patients. AA occur three times more frequently in ACHD compared to the general population. When complicating ACHD, AA convey a twofold increase in the risk for stroke, contributing to an up to 100-fold higher prevalence of stroke in the ACHD population compared to age-matched healthy controls. At present, the European Society of Cardiology (ESC) Guidelines suggest oral anticoagulation (OAC) in all adult patients with AA and intracardiac repair, cyanosis, Fontan palliation, or systemic right ventricle. In the remaining ACHD patients with AA, OAC is suggested if CHA2DS2-Vasc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score is ≥1 (Class of recommendation IIa, level of evidence C).

Non-vitamin K oral anticoagulants (NOACs) are increasingly preferred over vitamin-K antagonists (VKAs) in most clinical scenarios due to improved safety (with regard to intracranial and other major bleeding) and efficacy (prevention of embolic stroke or systemic embolism) along with the convenience they offer for patients and physicians (fixed dose, no food and drug interactions, no INR monitoring). On the other hand, scarce data is available on the use of NOAC in ACHD.

In order to address this gap in evidence, we propose a prospective multicenter single arm, observational cohort trial, which will provide data on the efficacy and safety of apixaban used for the prevention of thromboembolism in ACHD patients with AA.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients aged ≥18 years.
2. Presence of congenital heart disease (intracardiac repair, cyanosis, Fontan palliation, or systemic right ventricle or other congenital heart disease).
3. Non-Valvular Atrial Arrhythmia (including at least one electrocardiographically documented episode).
4. Signed written informed consent by the patient for participation in the study and agreement to comply with the medication and the follow-up schedule.

Exclusion Criteria:

1. moderate-to-severe mitral stenosis or mechanical valves
2. patient unwilling or unable to complete follow-up procedures

Primary outcomes:
measure: Stroke, systemic or pulmonary arterial thromboembolism and intracardiac thrombosis.
timeFrame: up to 58 months
measure: Major bleeding
timeFrame: up to 58 months
Secondary outcomes:
measure: Transient ischemic attack
timeFrame: up to 58 months
measure: Myocardial infarction
timeFrame: up to 58 months
measure: Death from cardiovascular causes
timeFrame: up to 58 months
measure: Τhe composite of major and clinically relevant nonmajor bleeding
timeFrame: up to 58 months
measure: Τhe composite of stroke, systemic or pulmonary arterial thromboembolism and intracardiac thrombosis, transient ischemic attack, myocardial infarction, or cardiovascular death
timeFrame: up to 58 months
Other outcomes:
measure: General quality of life
timeFrame: Baseline
measure: Apixaban persistence
timeFrame: up to 58 months
measure: Apixaban adherence
timeFrame: up to 58 months
Locations:
city: Athens
country: Greece
facility: Attikon University Hospital
city: Athens
country: Greece
facility: Mitera Children's Hospital
city: Athens
country: Greece
facility: Onassis Cardiac Surgery Centre
city: Thessaloníki
country: Greece
facility: AHEPA University Hospital
Study officials:
affiliation: AHEPA University Hospital
name: Georgios Giannakoulas, MD, PhD
role: STUDY_CHAIR
References:
citation: Kartas A, Doundoulakis I, Ntiloudi D, Koutsakis A, Kosmidis D, Rampidis G, Apostolopoulou S, Frogoudaki A, Tzifa A, Avramidis D, Ntzoyvara O, Liori S, Mousiama T, Mouratoglou SA, Karvounis H, Giannakoulas G. Rationale and design of a prospective, observational, multicentre study on the safety and efficacy of apixaban for the prevention of thromboembolism in adults with congenital heart disease and atrial arrhythmias: the PROTECT-AR study. BMJ Open. 2020 Sep 22;10(9):e038012. doi: 10.1136/bmjopen-2020-038012.