Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02741349 |
| Other study ID # |
2014-A00280-47 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 27, 2015 |
| Est. completion date |
January 2026 |
Study information
| Verified date |
January 2024 |
| Source |
Saint Antoine University Hospital |
| Contact |
Ariel Cohen, MD, PhD |
| Phone |
+33149282886 |
| Email |
ariel.cohen[@]aphp.fr |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The aim of the present prospective study is to further develop and validate a composite risk
score predicting both ischemic and bleeding risk, based on epidemiologic, clinical,
biological, and/or morphologic complementary data. First, the investigators will assess the
predictive performance of current clinical risk scores. Second, the investigators will assess
the potential predictive value of additional markers. Third, the investigators will aim to
develop a new risk score.
Description:
Patients with Atrial Fibrillation (AF) have an excessive risk of arterial thromboembolic
disease and heart failure, resulting in higher rates of cardiovascular and all-cause
mortality in this population.
Prevalence and incidence of Non-Valvular AF (NVAF) is rapidly increasing across developed
countries. cardiovascular (CV) and all-cause mortality rates related to AF have increased
between 1990 and 2010, irrespective of sex.
Determinants of AF (heart disease and/or cardiovascular risk factors), are themselves
associated with an excess risk of cardiovascular events.
Primary prevention of NVAF relies on the control of modifiable risk factors, such as
overweight, arterial hypertension, diabetes, and tobacco consumption which are associated
with the risk of AF risk and its complications.
Preventive treatment of cardiovascular complications is based on anti-thrombotic treatment,
which reduces the global ischemic risk but at the expense of an increase of bleeding risk.
Treatment decisions are guided by the evaluation of ischemic and hemorrhagic risks, as
determined by clinical scores (like CHADS2; CHA2DS2-VASc; HAS-BLED) that have been validated
on varying populations through retrospective cohort studies. However, since their
publication, these clinical scores have been criticized regarding their predictive value, the
lack of precision in the definition of their component and the threshold defined for
treatment decisions. Furthermore, several studies have demonstrated the interest of
biomarkers in addition to clinical parameters to predict the risk of cardiovascular
complications in AF. For example, preliminary data suggest that the dosage of Brain-type
natriuretic peptide (BNP), N-terminal (NT) Pro-BNP, troponin, C-reactive protein (CRP), and
all indicators whose levels increase independently of their usual causes may contribute to a
better prediction of cardiovascular complications including all-cause mortality in NVAF. Of
note, the rate of major bleeding events was very low (1.5 per cent among 3,978 patients from
the Euro Heart Survey on AF with complete follow-up) in the HAS-BLED validation cohort.
We hypothesize that epidemiologic, clinical, biologic, and morphologic complimentary data
could improve the stratification of cardiovascular risk in NVAF. Biologic and
echocardiographic approaches, in particular, could improve the performance of routinely used
clinical scores. Consequently, identification of a state of inflammation, hypercoagulability,
or increased circulating concentrations of certain biomarkers could explain the increased
risk of cardiovascular events in AF. Furthermore, the morphologic repercussions of NVAF,
including left atrium dilation and left ventricular systolic dysfunction, as well as the
presence of left atrial appendage stasis indicators, could also help refine the risk
stratification.
In a previous retrospective survey, the investigators have shown that biomarkers and
echomarkers could better stratify AF patients at increased cardiovascular risk. However, due
to its retrospective design and the lack of completeness, the investigators could not
validate a new risk score including all these markers and taking into account both
thromboembolic and hemorrhagic risk. Indeed, these usual biologic and morphologic parameters
will be obtained at admission in all patients in a prospective design.
There are three study sites.
Professor Ariel COHEN is the coordinating investigator of the study. A Clinical Research
Associate working within the Cardiology Service of the Saint-Antoine Hospital will monitor
the study.
The study duration is 5 years:
- Inclusion period: 3 years
- End of study: 2 years after the end of inclusion period
- Follow-up: the follow-up period will run for 2 years.
Inclusion: The inclusion visit will occur during the patient's hospitalization for NVAF in
the Cardiology Department. At the inclusion visit, information will be collected regarding
the patient's history of clinical events, current risk factors and treatments.
Follow-up: After hospital discharge, each patient will be seen every six month throughout the
two year follow-up period.
During the follow-up period, information on clinical events, changes in risk factors and
treatments occurring since the last follow-up contact will be collected for each patient, a
blood sample will be collected, and an echocardiography will be conducted.
Classification of preceding events and follow-up information will be supported by both
clinical exams and medical file evaluation. Interviews with general practitioners and the
patients themselves will also be used in order to collect all necessary information. In the
event of hospitalization, hospitalization reports will be collected. In cases of events
without hospitalization, general practitioner correspondence and prescription records will be
collected.
Patients with NVAF will receive anti-thrombotic treatment, in accordance with routine care
and European society of cardiology (ESC) guidelines.
The choice of anti-thrombotic treatment will be entirely at the discretion of the attending
physician during hospitalization.
Information describing all treatments received by each patient will be collected throughout
the study, from the inclusion visit to the final follow-up contact.
All echocardiographic procedures will be performed in the echocardiographic laboratory of
each Cardiology Department. Cardiologists specialized in echocardiographic examination will
perform all echocardiographic procedures.
Each participant will undergo an echocardiographic examination at their inclusion and at each
follow-up visit occurring every 6 months. The objective of the echocardiographic examinations
is the identification of cardiac conditions and diseases that may be associated with AF.
Primary Outcome variables The primary outcome variable is a composite cardiovascular endpoint
including stroke, transitory ischemic attack, thromboembolism, acute heart failure, acute
coronary syndrome, major bleeding and cardiovascular and all-cause mortality.
(Major bleeding will be defined according to international society on thrombosis and
haemostasis (ISTH) criteria)
Secondary Outcome variables
The incidence of each of the following events will be determined:
- death (all-cause and cardiovascular)
- acute heart failure
- stroke
- acute coronary syndrome
- major bleeding episodes
Enrolled participants will be included in the analysis. Participants who withdrew their
consent will be excluded from any analysis. Participants who had no event or those who were
lost to follow-up (impossibility of contact for more than 24 months) will be included up to
the date of their last contact.
Event free survival is defined as the time period from the day of enrollment in the study to
the day of the event or death.
Overall survival will be calculated for each patient starting at their enrollment until their
death or the end of follow-up. One analysis per event type will be conducted.
One vital status research will be conducted for each participant lost to follow-up; where
appropriate a cause of death research will be undertaken. To deal with the possibility for a
same patient to present multiple events, we will consider competing risk models.
