Congenital Heart DiseasePROTECT_ARNCT03854149
Apixaban in Adults With Congenital Heart Disease and Atrial Arrhythmias: the PROTECT-AR Study
An observational study of Congenital Heart Disease and Atrial Arrhythmia, run by AHEPA University Hospital at 4 sites in Greece.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Congenital Heart Disease, Atrial Arrhythmia, Thromboembolism
- How many people
- 218 participants
- Where
- 4 sitesGreece
- Study dates
- 1 Jul 2019to 30 May 2023
- How long will I take part?
- 24 Months
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- Male or female patients aged ≥18 years.
- Presence of congenital heart disease (intracardiac repair, cyanosis, Fontan palliation, or systemic right ventricle or other congenital heart disease).
- Non-Valvular Atrial Arrhythmia (including at least one electrocardiographically documented episode).
- Signed written informed consent by the patient for participation in the study and agreement to comply with the medication and the follow-up schedule.
Who cannot join
- moderate-to-severe mitral stenosis or mechanical valves
- patient unwilling or unable to complete follow-up procedures
Trial locations and contacts
4 sites in 1 country.
Greece4 sites
Attikon University Hospital
Athens, 12462
Mitera Children's Hospital
Athens, 15123
Onassis Cardiac Surgery Centre
Athens, 17674
AHEPA University Hospital
Thessaloniki, 54636
About this 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
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)
Read the 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.
- 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
- Medical subject headings
- Heart Defects, Congenital, Thromboembolism, Atrial Fibrillation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Adults with CHD & non-valvular atrial arrhythmias | Adults with congenital heart disease and non-valvular atrial arrhythmias (atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stroke, systemic or pulmonary arterial thromboembolism and intracardiac thrombosis.
The composite endpoint of all-cause stroke, systemic and pulmonary embolism and intracardiac thrombosis
Measured: up to 58 months
Major bleeding
Defined as clinically overt bleeding that is associated with:
- A fall in hemoglobin of 2 g/dL or more
- A transfusion of ≥2 units of packed red blood cells or whole blood
- Bleeding in a critical site: intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal
- Death (fatal bleeding)
Measured: up to 58 months
Secondary outcomes (5)
Transient ischemic attack
Defined as new neurologic symptoms or deficit lasting less than 24 hours with no new infarction on neuroimaging (if available).
Measured: up to 58 months
Myocardial infarction
Defined as the detection of a significant rise/fall of Troponin in association with symptoms of ischemia, ECG changes, proof of ischemia on imaging or intracoronary thrombus at angiography. [Fourth definition of myocardial infarction; European Society of Cardiology (ESC) 2018]
Measured: up to 58 months
Death from cardiovascular causes
Cardiovascular deaths were classified as deaths due to: ischemic stroke, hemorrhagic stroke, systemic or pulmonary embolism, other cardiovascular (i.e., myocardial infarction, sudden death, heart failure) and unobserved deaths.
Measured: up to 58 months
Τhe composite of major and clinically relevant nonmajor bleeding
Clinically relevant nonmajor bleeding bleeding=bleeding that is clinically overt, that satisfies none of the additional criteria required for the event to be adjudicated as a major bleeding event, that led to either hospital admission for bleeding, physician-guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy.
Measured: up to 58 months
Τhe composite of stroke, systemic or pulmonary arterial thromboembolism and intracardiac thrombosis, transient ischemic attack, myocardial infarction, or cardiovascular death
Measured: up to 58 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2019
- Study start1 Jul 2019
- Primary completion30 Apr 2023
- Study completion30 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 218 participants (actual)
- Target duration
- 24 Months
Sponsor and investigators
- Lead sponsor
- AHEPA University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Onassis Cardiac Surgery Centre, Attikon Hospital, MITERA Children's Hospital
- Responsible party
- Principal investigator, George Giannakoulas, AHEPA University Hospital
- Investigators
- Georgios Giannakoulas, MD, PhD, Study chair, AHEPA University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03854149
- Sponsor's protocol ID
- PROTECT_AR_trial_01102018_v1.0
- Acronym
- PROTECT_AR
- Status last verified
- Jun 2023
- First submitted
- 23 Feb 2019
- Last updated
- 22 Jun 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kartas A, Papazoglou AS, Moysidis DV, Despotopoulos S, Baroutidou A, Kosmidis D, Koutsakis A, Liori S, Apostolopoulou S, Frogoudaki A, Tzifa A, Galatas A, Alexandridis G, Spiridonidis E, Doundoulakis I, Karagiannidis E, Karvounis H, Ziakas A, Giannakoulas G. Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study. Int J Cardiol. 2024 Jul 1;406:131993. doi: 10.1016/j.ijcard.2024.131993. Epub 2024 Mar 31.
PubMed 38565389Kartas 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.
PubMed 32963069
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03854149
- Acronym / sponsor ID
- PROTECT_AR / PROTECT_AR_trial_01102018_v1.0
- 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
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 218 participants (actual)
- Lead sponsor
- AHEPA University HospitalUniversity, hospital or other
- Collaborators
- Onassis Cardiac Surgery Centre, Attikon Hospital, MITERA Children's Hospital
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 30 Apr 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 26 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 24 Months
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adults with CHD & non-valvular atrial arrhythmias | – | –Adults with congenital heart disease and non-valvular atrial arrhythmias (atrial fibrillation, atrial flutter or intra-atrial re-entrant tachycardia) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (4 listed)
- Male or female patients aged ≥18 years.
- Presence of congenital heart disease (intracardiac repair, cyanosis, Fontan palliation, or systemic right ventricle or other congenital heart disease).
- Non-Valvular Atrial Arrhythmia (including at least one electrocardiographically documented episode).
- Signed written informed consent by the patient for participation in the study and agreement to comply with the medication and the follow-up schedule.
Key exclusion criteria (2 listed)
- moderate-to-severe mitral stenosis or mechanical valves
- patient unwilling or unable to complete follow-up procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Stroke, systemic or pulmonary arterial thromboembolism and intracardiac thrombosis.
Time frame: up to 58 months
The composite endpoint of all-cause stroke, systemic and pulmonary embolism and intracardiac thrombosis
Major bleeding
Time frame: up to 58 months
Defined as clinically overt bleeding that is associated with: * A fall in hemoglobin of 2 g/dL or more * A transfusion of ≥2 units of packed red blood cells or whole blood * Bleeding in a critical site: intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal * Death (fatal bleeding)
5 secondary outcomes
Transient ischemic attack
Time frame: up to 58 months
Myocardial infarction
Time frame: up to 58 months
Death from cardiovascular causes
Time frame: up to 58 months
Τhe composite of major and clinically relevant nonmajor bleeding
Time frame: up to 58 months
Τhe composite of stroke, systemic or pulmonary arterial thromboembolism and intracardiac thrombosis, transient ischemic attack, myocardial infarction, or cardiovascular death
Time frame: up to 58 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2023.
- Derived from this study: PubMed 38565389Kartas A, Papazoglou AS, Moysidis DV, Despotopoulos S, Baroutidou A, Kosmidis D, Koutsakis A, Liori S, Apostolopoulou S, Frogoudaki A, Tzifa A, Galatas A, Alexandridis G, Spiridonidis E, Doundoulakis I, Karagiannidis E, Karvounis H, Ziakas A, Giannakoulas G. Use of apixaban in adults with congenital heart disease and atrial arrhythmias: The PROTECT-AR study. Int J Cardiol. 2024 Jul 1;406:131993. doi: 10.1016/j.ijcard.2024.131993. Epub 2024 Mar 31.
- Derived from this study: PubMed 32963069Kartas 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Georgios Giannakoulas, MD, PhD study chair
AHEPA University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Heart Disease and Atrial Arrhythmia, run by AHEPA University Hospital at 4 sites in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stroke, systemic or pulmonary arterial thromboembolism and intracardiac thrombosis. (time frame: up to 58 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03854149, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2023.