PMID- 31446143

OWN - NLM
STAT- Publisher
LR - 20190825
IS - 1559-2030 (Electronic)
IS - 1551-7144 (Linking)
DP - 2019 Aug 22
TI - 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).
PG - 105835
LID - S1551-7144(19)30550-6 [pii]
LID - 10.1016/j.cct.2019.105835 [doi]
AB - 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 P2Y12 receptor antagonist that inhibits platelet activation and
aggregation. Although ticagrelor was well tolerated in two phase 2 studies in
children and young adults with SCD, larger and longer-term treatment studies
are
needed to assess ticagrelor's efficacy to reduce VOCs. HESTIA3 will evaluate
the
efficacy, safety, and tolerability of ticagrelor versus placebo over a
minimum of
1year (maximum 2years) in pediatric patients with SCD. METHODS: Approximately
180
patients (aged >/=2 to <18years) 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.
CI - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Heeney, Matthew M
AU - Heeney MM
AD - Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical
School, 300 Longwood Ave, Boston, MA 02115, USA. Electronic address:
matthew.heeney@childrens.harvard.edu.
FAU - Abboud, Miguel R
AU - Abboud MR
AD - American University of Beirut Medical Center, Cairo Street, Beirut, Lebanon.
Electronic address: ma56@aub.edu.lb.
FAU - Amilon, Carl
AU - Amilon C
AD - Early Clinical Development, IMED Biotech Unit AstraZeneca, Gothenburg,
Pepparedsleden 1, Molndal 431 83, Sweden. Electronic address:
carl.amilon@astrazeneca.com.
FAU - Andersson, Marielle
AU - Andersson M
AD - BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Pepparedsleden 1, Molndal
431
83, Sweden. Electronic address: Marielle.Andersson@astrazeneca.com.
FAU - Githanga, Jessie
AU - Githanga J
AD - Hematology and Blood Transfusion Unit, Department of Human Pathology,
University
of Nairobi, P. O. Box 19676, Nairobi 00202, Kenya. Electronic address:
jessie.githanga@uonbi.ac.ke.
FAU - Inusa, Baba
AU - Inusa B
AD - Paediatric Hematology, Guy's and St Thomas' NHS Trust, Evelina London
Children's
Hospital, Westminster Bridge Rd, Lambeth, London SE1 7EH, UK. Electronic
address:
Baba.Inusa@gstt.nhs.uk.
FAU - Kanter, Julie
AU - Kanter J
AD - Hematology-Oncology, Department of Medicine, University of Alabama at
Birmingham,
2000 6th Avenue S, Birmingham, AL 35233, USA. Electronic address:
kanter@musc.edu.
FAU - Leonsson-Zachrisson, Maria
AU - Leonsson-Zachrisson M
AD - BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Pepparedsleden 1, Molndal
431
83, Sweden. Electronic address: Maria.Leonsson-Zachrisson@astrazeneca.com.
FAU - Michelson, Alan D
AU - Michelson AD
AD - Center for Platelet Research Studies, Division of Hematology/Oncology, Boston
Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Karp 08213,
Boston, MA 02115, USA. Electronic address:
Alan.Michelson@childrens.harvard.edu.
FAU - Berggren, Anders R
AU - Berggren AR
AD - BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Pepparedsleden 1, Molndal
431
83, Sweden. Electronic address: anders.r.berggren@astrazeneca.com.
CN - HESTIA3 study investigators
LA - eng
SI - ClinicalTrials.gov/NCT03615924
PT - Journal Article
DEP - 20190822
PL - United States
TA - Contemp Clin Trials
JT - Contemporary clinical trials
JID - 101242342
SB - IM
OTO - NOTNLM
OT - Antiplatelet therapy
OT - Pediatric
OT - Sickle cell disease
OT - Ticagrelor
OT - Vaso-occlusive crisis
EDAT- 2019/08/26 06:00
MHDA- 2019/08/26 06:00
CRDT- 2019/08/26 06:00
PHST- 2019/03/15 00:00 [received]
PHST- 2019/08/19 00:00 [revised]
PHST- 2019/08/20 00:00 [accepted]
PHST- 2019/08/26 06:00 [entrez]
PHST- 2019/08/26 06:00 [pubmed]
PHST- 2019/08/26 06:00 [medline]
AID - S1551-7144(19)30550-6 [pii]
AID - 10.1016/j.cct.2019.105835 [doi]
PST - aheadofprint
SO - Contemp Clin Trials. 2019 Aug 22:105835. doi: 10.1016/j.cct.2019.105835.