Clinical trial NCT03846297: Optimisation of Decision Making for Defibrillator Implantation in Hypertrophic Cardiomyopathy
Official title: Optimisation of Decision Making for Defibrillator Implantation in Hypertrophic Cardiomyopathy
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypertrophic Cardiomyopathy
Keywords: hypertrophic cardiomyopathy
implantable cardioverter defibrillator
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2019-02-19
Enrollment: 2000
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: * Inclusion of adults with HCM, as well as teenagers 16 or older since SCD occurs frequently in this age group
* Necessary not to include specific etiologies such as amyloidosis because of a known different prognosis and natural history
* Necessary not to include patients with ICD as secondary prevention because of a different prognosis and a worldwide consensus on the need for ICD implantation in this case
* Necessary to include all cases whatever their date of diagnosis as the predictive modelling (primary objective) targets the actual population being followed up in real life, and will ultimately be applied on this population

Brief summary: The main objective of the study is to improve implantable cardioverter defibrillator (ICD) implantation decision-making processing relevance by developing a new prediction model of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM), including newly identified potential biomarkers by magnetic resonance imaging (MRI) and genetics, through a prospective nationwide study, multivariate analysis and modelling of an absolute risk.

The secondary objective is to perform a medico-economic analysis of ICD implantation in order to define an optimal rule for ICD implantation in patients with HCM, taking into account the benefits of ICD, adverse effects of ICD and associated costs (cost of quality adjusted life years saved).

Detailed description: HCM is a genetic disease, usually autosomal dominant, with a prevalence of about 1/500 in the general population. HCM represents a major cause of SCD in the young, and is the first cause of SCD in athletes less than 35 years of age. The only efficient prevention of SCD, apart from exercise restriction, is ICD.

Given this dreadful potential outcome of HCM, the identification of patients that should receive an ICD is of paramount importance. However, the indications for ICD are controversial and very different guidelines are currently available, coming from the American society of Cardiology, the French Haute Autorité de Santé and from the European society of Cardiology. In addition, these guidelines are all based on retrospective studies and have major limitations. The situation faces a critical need of improvement. Thus, this study has been designed with the objective to propose a revision of international recommendations for defibrillator implantation in HCM patients.

This prospective multicenter non-interventional single-arm study is planned to be conducted in 40 sites with a collection of clinical and biological data, carried out as required for the usual management and care of patients. No investigation will be performed specifically for this study except for an additional blood sample collection at baseline during routine outpatient care and annual interview during follow-up.

Eligibility criteria: Inclusion Criteria:

* Patient with a diagnosis of HCM based on conventional criteria (left ventricle wall thickness ≥ 15 mm in adult index or ≥ 13 mm in adult relatives) in the absence of abnormal loading conditions
* Aged ≥ 16 years
* Patient without or with a defibrillator (in this latter case it should have been implanted for primary prevention, not for secondary prevention)
* Affiliation to a social security insurance

Exclusion Criteria:

* Specific etiologies such as amyloidosis
* Patients with ICD as secondary prevention (after aborted SCD or sustained ventricular arrhythmia)

Primary outcomes:
measure: Improvement of the ability to predict major clinical events: C-index comparisons
timeFrame: throughout of the study, an average of 1 year
Secondary outcomes:
measure: Cost-effectiveness study
timeFrame: throughout of the study, an average of 1 year
measure: Cost-utility analysis
timeFrame: throughout of the study, an average of 1 year
measure: Quality Adjusted Life Years
timeFrame: at baseline and at 6-year follow-up
measure: Improvement of the ability to predict major clinical events: C-index comparisons
timeFrame: at baseline
Other outcomes:
Locations:
city: Boulogne Billancourt
country: France
facility: Centre de référence pour les cardiomyopathies et les troubles du rythme héréditaires ou rares - UF de Génétique, Hôpital Ambroise Paré,
state: Hauts-de-Seine
Study officials:
affiliation: Centre de référence maladies cardiaques héréditaires, Hôpital Ambroise Paré & Hôpital Pitié-Salpêtrière
name: Philippe CHARRON, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: