Ticagrelor versus placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: Rationale and design of a randomized, double-blind, parallel-group, multicenter phase 3 study (HESTIA3).
Adolescent
Anemia, Sickle Cell
/ complications
Child
Child, Preschool
Clinical Trials, Phase III as Topic
Double-Blind Method
Female
Humans
Male
Multicenter Studies as Topic
Platelet Aggregation Inhibitors
/ therapeutic use
Randomized Controlled Trials as Topic
Research Design
Ticagrelor
/ therapeutic use
Antiplatelet therapy
Pediatric
Sickle cell disease
Ticagrelor
Vaso-occlusive crisis
Journal
Contemporary clinical trials
ISSN: 1559-2030
Titre abrégé: Contemp Clin Trials
Pays: United States
ID NLM: 101242342
Informations de publication
Date de publication:
10 2019
10 2019
Historique:
received:
15
03
2019
revised:
19
08
2019
accepted:
20
08
2019
pubmed:
26
8
2019
medline:
22
10
2020
entrez:
26
8
2019
Statut:
ppublish
Résumé
An unmet need for therapies exists to reduce sickle cell disease (SCD) complications in pediatric patients. Activated platelets contribute to the formation of cellular aggregates during sickling and vaso-occlusive crises (VOCs). Ticagrelor is an oral, direct-acting, and reversible adenosine diphosphate P2Y Approximately 180 patients (aged ≥ 2 to <18 years) with SCD (≥ 2 VOCs in the prior year) from 18 countries will be randomized 1:1 to ticagrelor or placebo. Primary endpoint: number of VOCs (a composite endpoint of painful crises and/or acute chest syndrome); key secondary endpoints: hospitalizations, pain intensity and analgesic use during VOCs, acceptability of formulation, and health-related quality of life. The weight-based doses of ticagrelor are set by modeling and simulation. Platelet inhibition data, measured by the vasodilator-stimulated phosphoprotein assay, will be collected for exploratory purposes. HESTIA3 aims to demonstrate that using greater target platelet inhibition than previous studies on SCD, ticagrelor will decrease the frequency of VOC in pediatric patients. Trial Identifier: NCT03615924; EudraCT2017-002421-38.
Sections du résumé
BACKGROUND
An unmet need for therapies exists to reduce sickle cell disease (SCD) complications in pediatric patients. Activated platelets contribute to the formation of cellular aggregates during sickling and vaso-occlusive crises (VOCs). Ticagrelor is an oral, direct-acting, and reversible adenosine diphosphate P2Y
METHODS
Approximately 180 patients (aged ≥ 2 to <18 years) with SCD (≥ 2 VOCs in the prior year) from 18 countries will be randomized 1:1 to ticagrelor or placebo. Primary endpoint: number of VOCs (a composite endpoint of painful crises and/or acute chest syndrome); key secondary endpoints: hospitalizations, pain intensity and analgesic use during VOCs, acceptability of formulation, and health-related quality of life. The weight-based doses of ticagrelor are set by modeling and simulation. Platelet inhibition data, measured by the vasodilator-stimulated phosphoprotein assay, will be collected for exploratory purposes.
CONCLUSIONS
HESTIA3 aims to demonstrate that using greater target platelet inhibition than previous studies on SCD, ticagrelor will decrease the frequency of VOC in pediatric patients. Trial Identifier: NCT03615924; EudraCT2017-002421-38.
Identifiants
pubmed: 31446143
pii: S1551-7144(19)30550-6
doi: 10.1016/j.cct.2019.105835
pii:
doi:
Substances chimiques
Platelet Aggregation Inhibitors
0
Ticagrelor
GLH0314RVC
Banques de données
ClinicalTrials.gov
['NCT03615924']
EudraCT
['2017-002421-38']
Types de publication
Clinical Trial Protocol
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
105835Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.