Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't Ppublish 13 citations
PubMed: 35849650 DOI: 10.1182/blood.2021014095
Ticagrelor vs placebo for the reduction of vaso-occlusive crises in pediatric sickle cell disease: the HESTIA3 study.
Blood 140(13):1470-1481
Authors: Matthew M Heeney, Miguel R Abboud, Jessie Githanga, Baba P D Inusa, Julie Kanter, Alan D Michelson, Videlis Nduba, Victor Musiime, Mohini Apte, Adlette Inati, Amar M Taksande, Marielle Andersson, Magnus Åstrand, Noha Maklad, Mohammad Niazi, Anders Himmelmann, Anders R Berggren
Affiliations
- Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
- American University of Beirut Medical Center, Beirut, Lebanon.
- Hematology and Blood Transfusion Unit, Department of Human Pathology, University of Nairobi, Nairobi, Kenya.
- Paediatric Haematology, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom.
- Hematology-Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.
- Center for Platelet Research Studies, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
- Kenya Medical Research Institute, Center for Respiratory Diseases Research, Nairobi, Kenya.
- Department of Pediatrics and Child Health, College of Health Sciences, Makerere University, Kampala, Uganda.
- Joint Clinical Research Centre, Kampala, Uganda.
- Department of Pediatrics, Government Medical College Nagpur, Nagpur, India.
- School of Medicine, Lebanese American University, Byblos and Nini Hospital, Tripoli, Lebanon.
- Department of Pediatrics, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashta, India.
- AstraZeneca BioPharmaceuticals R&D, Late-stage Development, Cardiovascular, Renal and Metabolic, Gothenburg, Sweden.
- AstraZeneca BioPharmaceuticals R&D, Clinical Pharmacology and Safety Sciences, Clinical Pharmacology and Quantitative Pharmacology, Cardiovascular, Renal and Metabolic, Gothenburg, Sweden; and.
- AstraZeneca BioPharmaceuticals R&D, Late-stage Development, Cardiovascular, Renal and Metabolic, Gaithersburg, MD.
Abstract
The phase 3 HESTIA3 study assessed the efficacy and safety of the reversible P2Y12 inhibitor ticagrelor vs placebo in preventing vaso-occlusive crises in pediatric patients with sickle cell disease (SCD). Patients aged 2 to 17 years were randomly assigned 1:1 to receive weight-based doses of ticagrelor or matching placebo. The primary end point was the rate of vaso-occlusive crises, a composite of painful crises and/or acute chest syndrome (ACS). Key secondary end points included number and duration of painful crises, number of ACS events, and number of vaso-occlusive crises requiring hospitalization or emergency department visits. Exploratory end points included the effect of ticagrelor on platelet activation. In total, 193 patients (ticagrelor, n = 101; placebo, n = 92) underwent randomization at 53 sites across 16 countries. The study was terminated 4 months before planned completion for lack of efficacy. Median ticagrelor exposure duration was 296.5 days. The primary end point was not met: estimated yearly incidence of vaso-occlusive crises was 2.74 in the ticagrelor group and 2.60 in the placebo group (rate ratio, 1.06; 95% confidence interval, 0.75-1.50; P = .7597). There was no evidence of efficacy for ticagrelor vs placebo across secondary end points. Median platelet inhibition with ticagrelor at 6 months was 34.9% predose and 55.7% at 2 hours' postdose. Nine patients (9%) in the ticagrelor group and eight patients (9%) in the placebo group had at least one bleeding event. In conclusion, no reduction of vaso-occlusive crises was seen with ticagrelor vs placebo in these pediatric patients with SCD. This trial was registered at www.clinicaltrials.gov as #NCT03615924.
MeSH
Cells, Hematology, Anemia, Sickle Cell, Ticagrelor, Blood Platelets, Vaso-Occlusive Crises
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