A dose‐ranging study of ticagrelor in children aged 3‐17 years with sickle cell disease: A 2‐part phase 2 study
Bibliographic record
Abstract
Abstract 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".