Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, Colorado, USA.
Pediatric Neurology and Concussion Center, Dent Neurologic Institute, Amherst, New York, USA.
Headache. 2022 Oct;62(9):1207-1217. doi: 10.1111/head.14391.
To evaluate the efficacy and safety of zolmitriptan nasal spray (ZNS) in the acute treatment of migraine headache in patients aged 6 to 11 years.
Triptans have demonstrated efficacy in adults, but pediatric studies of these agents have largely failed and there are few triptan options for these patients. Because lack of response to 1 triptan does not necessarily preclude response to an alternate triptan, additional triptan options for pediatric patients are desirable.
This Phase 3, randomized, double-blind, placebo-controlled, multicenter crossover trial with an open-label extension enrolled patients aged 6 to 11 years with a diagnosis of migraine for ≥6 months and ≥16 headache-free days/month (N = 373). After a run-in period to eliminate placebo responders, 186 patients were randomized within their body weight stratum to ZNS followed by matching placebo, or placebo followed by matching ZNS. Patients <50 kg who were randomly allocated to ZNS were randomized to 5:1 to ZNS 2.5 or 1.0 mg; those ≥50 kg were randomized 5:1 to ZNS 5.0 or 2.5 mg. Patients had 6 weeks to treat 1 moderate to severe migraine headache and then crossed over to the alternate arm, during which they had 6 weeks to treat a second migraine attack. Patients could participate in a subsequent 6-month outpatient open-label extension. The primary efficacy endpoint was pain-free status at 2 h in patients treated with the high dose from each stratum.
The trial was terminated early due to slow enrollment. Three hundred patients (mean age, 9 years) entered the placebo run-in period and 186 entered the double-blind period. Pain-free status at 2 h postdose was achieved by 45/133 (33.8%) and 30/128 (23.4%) of patients who received high-dose ZNS and placebo, respectively (p = 0.0777; odds ratio [OR] 1.51; 95% confidence interval [CI] 0.96, 2.38). Several secondary endpoints achieved statistical significance. There were few treatment-related adverse events and none led to discontinuation. ZNS retained efficacy and demonstrated a consistent safety profile throughout the 6-month open-label extension.
The effect of high-dose ZNS on the primary endpoint of pain-free status at 2 h did not achieve statistical significance. ZNS was safe and well tolerated in this pediatric population.
评估佐米曲普坦鼻喷雾剂（ZNS）在 6 至 11 岁偏头痛急性治疗中的疗效和安全性。
曲坦类药物在成人中已被证明有效，但这些药物的儿科研究大多失败，这些患者的曲坦类药物选择很少。由于对 1 种曲坦类药物无反应并不一定排除对另一种曲坦类药物的反应，因此需要为儿科患者提供更多的曲坦类药物选择。
这是一项 3 期、随机、双盲、安慰剂对照、多中心交叉试验，设有开放标签扩展期，纳入了 6 至 11 岁、偏头痛诊断≥6 个月且每月≥16 天无头痛（N=373）的患者。在为期 1 周的洗脱期以排除安慰剂反应者后，根据体重分层将 186 名患者随机分为 ZNS 组（随后给予匹配安慰剂）或安慰剂组（随后给予匹配 ZNS）。体重<50kg 的患者随机分配至 ZNS 5:1 组，随机分配至 ZNS 2.5mg 或 1.0mg；体重≥50kg 的患者随机分配至 ZNS 5:1 组，随机分配至 ZNS 5.0mg 或 2.5mg。患者有 6 周的时间治疗 1 次中度至重度偏头痛发作，然后交叉至另一臂，在此期间他们有 6 周的时间治疗第 2 次偏头痛发作。患者可以参加随后的 6 个月门诊开放标签扩展期。主要疗效终点是每个剂量分层中接受高剂量治疗的患者在 2 小时时的无痛状态。
由于入组速度缓慢，试验提前终止。300 名患者（平均年龄 9 岁）进入安慰剂洗脱期，186 名患者进入双盲期。接受高剂量 ZNS 和安慰剂的患者在 2 小时时达到无痛状态的比例分别为 45/133（33.8%）和 30/128（23.4%）（p=0.0777；优势比[OR]1.51；95%置信区间[CI]0.96，2.38）。几个次要终点达到了统计学意义。治疗相关不良事件较少，无事件导致停药。ZNS 在整个 6 个月的开放标签扩展期内保持疗效并表现出一致的安全性。
高剂量 ZNS 对 2 小时无痛状态这一主要终点的影响未达到统计学意义。ZNS 在儿科人群中是安全且耐受良好的。
