PMID- 30187935
OWN - NLM
STAT- MEDLINE
DCOM- 20190819
LR  - 20231004
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Print)
IS  - 0361-8609 (Linking)
VI  - 93
IP  - 12
DP  - 2018 Dec
TI  - A dose-ranging study of ticagrelor in children aged 3-17 years with sickle cell 
      disease: A 2-part phase 2 study.
PG  - 1493-1500
LID - 10.1002/ajh.25273 [doi]
AB  - Antiplatelet treatment is a potential therapeutic approach for sickle cell 
      disease (SCD). Ticagrelor inhibits platelet aggregation and is approved for 
      adults with acute coronary syndrome and following myocardial infarction. HESTIA1 
      (NCT02214121) was a 2-part, phase 2 dose-finding study generating ticagrelor 
      exposure, platelet inhibition, and safety data in children with SCD (3-17 years). 
      In part A (n = 45), patients received 2 ticagrelor single doses, 0.125-2.25 mg/kg 
      (washout >/=7 days), then 7 days of twice-daily (bid) dosing with 0.125, 0.563, or 
      0.75 mg/kg. In the 4-week blinded Part B extension (optional), patients received 
      ticagrelor (0.125, 0.563, or 0.75 mg/kg bid; n = 16) or placebo (n = 7). Platelet 
      reactivity decreased from baseline to 2 hours postdosing, and returned to near 
      baseline after 6 hours postdosing. Dose-dependent platelet inhibition was seen 
      with ticagrelor; mean relative P2Y(12) reaction unit inhibition 2 hours after a 
      single dose ranged from 6% (0.125 mg/kg) to 73% (2.25 mg/kg). Ticagrelor plasma 
      exposure increased approximately dose proportionally. No patients experienced a 
      hemorrhagic event during treatment. No differences were seen between groups in 
      pain ratings and analgesic use during Part B. Ticagrelor was well tolerated with 
      no safety concerns, no discontinuations due to adverse events (AEs), and reported 
      AEs were mainly due to SCD. In conclusion, a dose-exposure-response relationship 
      for ticagrelor was demonstrated in children with SCD for the first time. These 
      data are important for future pediatric studies of the efficacy and safety of 
      ticagrelor in SCD.
CI  - (c) 2018 The Authors. American Journal of Hematology published by Wiley 
      Periodicals, Inc.
FAU - Hsu, Lewis L
AU  - Hsu LL
AUID- ORCID: 0000-0002-3156-2378
AD  - Children's Hospital University of Illinois, Chicago, Illinois.
FAU - Sarnaik, Sharada
AU  - Sarnaik S
AD  - Children's Hospital of Michigan, Detroit, Michigan.
FAU - Williams, Suzan
AU  - Williams S
AD  - Hospital for Sick Children, Toronto, Ontario, Canada.
FAU - Amilon, Carl
AU  - Amilon C
AD  - Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech 
      Unit, AstraZeneca, Gothenburg, Sweden.
FAU - Wissmar, Jenny
AU  - Wissmar J
AD  - Global Medicine Development, AstraZeneca, Gothenburg, Sweden.
FAU - Berggren, Anders
AU  - Berggren A
AD  - Global Medicine Development, AstraZeneca, Gothenburg, Sweden.
CN  - HESTIA1 Investigators
LA  - eng
SI  - ClinicalTrials.gov/NCT02214121
GR  - AstraZeneca/International
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181002
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (Platelet Aggregation Inhibitors)
RN  - GLH0314RVC (Ticagrelor)
MH  - Adolescent
MH  - Anemia, Sickle Cell/*drug therapy
MH  - Child
MH  - Child, Preschool
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Humans
MH  - Platelet Aggregation/drug effects
MH  - Platelet Aggregation Inhibitors/administration & dosage
MH  - Platelet Function Tests
MH  - Ticagrelor/*administration & dosage/therapeutic use
MH  - Treatment Outcome
PMC - PMC6282821
EDAT- 2018/09/07 06:00
MHDA- 2019/08/20 06:00
PMCR- 2018/12/06
CRDT- 2018/09/07 06:00
PHST- 2018/06/25 00:00 [received]
PHST- 2018/08/28 00:00 [revised]
PHST- 2018/08/30 00:00 [accepted]
PHST- 2018/09/07 06:00 [pubmed]
PHST- 2019/08/20 06:00 [medline]
PHST- 2018/09/07 06:00 [entrez]
PHST- 2018/12/06 00:00 [pmc-release]
AID - AJH25273 [pii]
AID - 10.1002/ajh.25273 [doi]
PST - ppublish
SO  - Am J Hematol. 2018 Dec;93(12):1493-1500. doi: 10.1002/ajh.25273. Epub 2018 Oct 2.