Clinical trial NCT03368261: Epidemiology and Pathophysiological Mechanisms of HTAP in SS and SC Children in Martinique and Guadeloupe.
Official title: Epidemiology and Pathophysiological Mechanisms of Pulmonary Arterial Hypertension in SS and SC Children in Martinique and Guadeloupe.Three Years Follow up of a Cohort of Children Aged From 8 to 16 Years Old
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sickle Cell Disease
Keywords: Pulmonary arterial hypertension
SCD
Epidemiology
Lead sponsor: Centre Hospitalier Universitaire de la Guadeloupe
Sponsor class: OTHER
First posted: 2017-12-11
Enrollment: 185
Sex: ALL
Minimum age (years): 8
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: pulmonary arterial hypertension (PAH) has been reported with a prevalence of approximately 30% in adult sickle cell disease (SCD) patients, with an increased mortality in SCD patients with PAH, compared with those without PAH. The identification of several hemolysis biomarkers such as lactate dehydrogenase, bilirubin, reticulocytes or hemoglobin level, has clearly documented a link between hemolysis and PAH. However, other physiopathological mechanisms may be involved to explain PAH in these patients, such as pulmonary thromboembolism, pulmonary fibrosis or left heart diastolic and / or systolic dysfunction.

The investigators suggest studying HTAP in patient's presenting the most frequent both drepanocytic syndromes, SS and SC and homogeneous in their medical coverage and the association between HTAP risk and specific SCD complications.

Detailed description: The primary aim of this study is to estimate the prevalence and the incidence of PAH in a population of SCD children (SS, SC) with similar medical caring, aged from 8 to 16 years old.

Unlike the important number of studies in SCD adults, very few SCD children studies were performed. None of these studies reported the mortality rate associated with PAH in children although the literature reported a decrease of this morbid-mortality comparing different medical caring of the patients. The investigators hypothesized that physiopathological mechanisms responsible for PAH had to be different in SCD children compared with adults, as most degenerative processes had no time enough to appear during children's lives. At the inclusion in our study the diagnosis of PAH will be performed by transthoracic Doppler-echocardiograms in a group of 306 children (aged between 8 to 16 years old) with either SS or SC genotype with similar medical caring, to avoid a known selection bias. These patients will be followed during a 3 years longitudinal period. The occurrence of the clinical specific complications associated with SCD (acute chest syndrome, painful vaso occlusive crisis, septicemia and stroke) and the observed mortality rate of our children group, will be compared in patients groups stratified according to the occurrence of PAH. The expression of several molecular and cellular genetic biomarkers potentially associated with this complication will also be studied.

Eligibility criteria: Inclusion Criteria:

* children aged between 8 to 16 years old,
* SS homozygote or SC compound heterozygote, followed by the sickle cell centers of Guadeloupe and Martinique or by the pediatric department of the university hospital of Fort-de-France, identified by the systematic neonatal screening programs performed in Guadeloupe and Martinique or by other labeled centers, registered in the French medical social security national program, and for which the parental and the old children consent has been obtained.

Exclusion Criteria:

* other hemoglobinopathies, chronic transfusion therapy programs or treatments which affected the expression of the biomarkers studied (unless hydroxyurea treatment),
* recent blood transfusion or phlebotomies (less than 3 months);
* patients not at steady state,
* pregnancy or breast feeding,
* refusal of parental and old children consent.

Primary outcomes:
measure: incidence of pulmonary arterial hypertension
timeFrame: Through study completion, an average of 5 years
Secondary outcomes:
measure: The association between PAH risk and specific SCD complications
timeFrame: Through study completion, an average of 5 years
Other outcomes:
Locations:
city: Fort-de-France
country: Martinique
facility: Hospital University Center of Martinique
Study officials:
affiliation: Hospital University Center of Pointe-à-Pitre
name: Maryse ETIENNE-JULAN, Doctor specializing in SCD
role: STUDY_DIRECTOR
References: