Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA.
American University of Beirut Medical Center, Beirut, Lebanon.
Blood. 2022 Sep 29;140(13):1470-1481. doi: 10.1182/blood.2021014095.
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.
HESTIA3 阶段 3 研究评估了可逆 P2Y12 抑制剂替卡格雷洛与安慰剂在预防小儿镰状细胞病 (SCD) 患者血管闭塞性危象中的疗效和安全性。年龄为 2 至 17 岁的患者以 1:1 的比例随机接受基于体重的替卡格雷洛或匹配的安慰剂剂量。主要终点是血管闭塞性危象的发生率，即疼痛危象和/或急性胸部综合征 (ACS) 的综合指标。关键次要终点包括疼痛危象的次数和持续时间、ACS 事件的次数以及需要住院或急诊就诊的血管闭塞性危象的次数。探索性终点包括替卡格雷洛对血小板活化的影响。在 16 个国家的 53 个地点，共有 193 名患者（替卡格雷洛组，n = 101；安慰剂组，n = 92）接受了随机分组。由于缺乏疗效，该研究在计划完成前 4 个月提前终止。替卡格雷洛暴露的中位持续时间为 296.5 天。主要终点未达到：替卡格雷洛组血管闭塞性危象的年估计发生率为 2.74，安慰剂组为 2.60（发生率比，1.06；95%置信区间，0.75-1.50；P =.7597）。替卡格雷洛与安慰剂在次要终点上均无疗效证据。替卡格雷洛在 6 个月时的中位血小板抑制率为预剂量的 34.9%，2 小时后为 55.7%。替卡格雷洛组有 9 名患者（9%）和安慰剂组有 8 名患者（9%）至少发生了一次出血事件。总之，在这些患有 SCD 的儿科患者中，与安慰剂相比，替卡格雷洛并未减少血管闭塞性危象的发生。该试验在 www.clinicaltrials.gov 上注册为 #NCT03615924。
