Epidemiology and Pathophysiological Mechanisms of HTAP in SS and SC Children in Martinique and Guadeloupe. (SAPOTILLE)

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

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Other: HTAP/ clinical complications in the sickle cell disease

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.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Martinique
  • Fort-de-France, Martinique, 97261
    • Hospital University Center of Martinique

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

OTHER: HTAP/ clinical complications in the sickle cell disease; Supply epidemiological data on this detected HTAP, and allow the characterization of the clinico-biological paintings and the mortality which are associated to them.

Other: HTAP/ clinical complications in the sickle cell disease; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
incidence of pulmonary arterial hypertension	The primary outcome of the present study is to estimate the incidence of pulmonary arterial hypertension documented by the presence of tricuspid regurgitation jet velocity of at least 2.5 ms-1 by Doppler echocardiographic assessment.	Through study completion, an average of 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between PAH risk and specific SCD complications	To determine the association between PAH risk and specific SCD complications (painful crisis, acute chest syndrome, severe infectious events, stroke, cerebral vasculopathy), expression of molecular (pro-PBN, nitrite/ nitrate compounds, sVCAM-1, sICAM-1, S- and P-selectine, plasmatic hemoglobin, ET-1, CD40L), cellular (microparticles, hemorheological parameters) biomarkers, and genetic markers (alpha-globin, type 3 NOS, endothélin-1, ACVRL1, BMPR2, BMP6). To determine if PAH is a risk factor of the clinical complications cited previously above and of mortality.	Through study completion, an average of 5 years

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Pointe-a-Pitre
• Investigators: Study Director: Maryse ETIENNE-JULAN, Doctor specializing in SCD, Hospital University Center of Pointe-à-Pitre

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 11, 2010
• Primary Completion (ACTUAL): October 2, 2013
• Study Completion (ACTUAL): October 17, 2016

Study Registration Dates

• First Submitted: December 1, 2017
• First Submitted That Met QC Criteria: December 5, 2017
• First Posted (ACTUAL): December 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): December 11, 2017
• Last Update Submitted That Met QC Criteria: December 5, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Epidemiology; SCD; Pulmonary arterial hypertension
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Hypertension, Pulmonary; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Pulmonary Arterial Hypertension; Anemia, Sickle Cell
• Other Study ID Numbers: RBM-PAP-2009/69

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No