Candesartan versus placebo for migraine prevention in patients with episodic migraine: a randomised, triple-blind, placebo-controlled, phase 2 trial.

This study aimed to evaluate the safety, tolerability, and efficacy of candesartan for the preventive treatment of episodic migraine.

本研究旨在评估坎地沙坦用于预防性治疗发作性偏头痛的安全性、耐受性和疗效。

Methods

This randomised, triple-blind, placebo-controlled, parallel-group, phase 2 trial was done at nine hospitals across Norway and one large hospital in Estonia, selected for their neurological services and research capacity.

这是一项在挪威的九家医院和爱沙尼亚的一家大型医院进行的随机、三盲、安慰剂对照、平行组的2期试验，这些医院因其神经学服务和研究能力而被选中。

Adults aged 18-64 years, experiencing between two and eight migraine attacks (with or without aura) per month were randomly assigned (1:1:1) to receive oral candesartan 16 mg, candesartan 8 mg, or placebo daily for 12 weeks.

年龄在18-64岁之间，每月经历2至8次偏头痛发作（有或无先兆）的成年人被随机分配（1:1:1），每天口服坎地沙坦16毫克、坎地沙坦8毫克或安慰剂，持续12周。

Acute migraine medication was permitted during the trial but the use of other preventive treatments were prohibited.

试验期间允许使用急性偏头痛药物，但禁止使用其他预防性治疗。

Participants, site personnel, and the trial statistician were all masked to treatment allocation.

参与者、现场人员和试验统计员均对治疗分配情况进行了盲法处理。

The primary endpoint was the change in the mean number of migraine days per 4 weeks from baseline to weeks 9-12, analysed in the intention-to-treatpopulation (participants with at least one post-baseline measurement during the masked treatment period).

主要终点是从基线到第9-12周，每4周偏头痛天数平均变化，分析在意向治疗人群中（在蒙蔽治疗期间至少有一次基线后测量的参与者）。

Safety analyses included all participants who received at least one dose of the trial drug.

安全性分析包括所有至少接受一次试验药物剂量的参与者。

This trial is registered with ClinicalTrials.gov (NCT04574713; Oct 5, 2020) and is completed.

该试验已在ClinicalTrials.gov注册（NCT04574713；2020年10月5日），并已完成。

Results

Between April 9, 2021, and April 12, 2024, 1340 individuals were assessed for eligibility, 806 were deemed ineligible, and 534 were enrolled in the trial. Of these, 77 were excluded, and 457 participants were randomly assigned to candesartan 16 mg (n=156), candesartan 8 mg (n=150), or placebo (n=151).

在2021年4月9日至2024年4月12日期间，共有1340名个体接受了资格评估，其中806名被认为不符合条件，534名被纳入试验。在这些参与者中，有77名被排除在外，剩余的457名参与者被随机分配到坎地沙坦16毫克组（n=156）、坎地沙坦8毫克组（n=150）或安慰剂组（n=151）。

The mean age of the trial population was 38·7 years (SD 10·0); 391 (86%) participants were female and 66 (14%) were male.

试验人群的平均年龄为38.7岁（标准差10.0）；391名（86%）参与者为女性，66名（14%）为男性。

The mean number of migraine days was 5·7 (SD 2·5) at baseline.

基线时，偏头痛的平均天数为5.7天（标准差2.5）。

By weeks 9-12, the reduction in migraine days was 2·04 days (95% CI 1·65-2·41 p<0·0001) in the candesartan 16 mg group compared with 0·82 days (0·38-1·23; p=0·0003) in the placebo group ((difference between groups -1·22 [95% CI -1·75 to -0·70]; p<0·0001).

在第9-12周，与安慰剂组相比，坎地沙坦16 mg组的偏头痛天数减少了2.04天（95% CI 1.65-2.41，p<0.0001），而安慰剂组减少了0.82天（0.38-1.23；p=0.0003），两组之间的差异为-1.22天（95% CI -1.75至-0.70；p<0.0001）。

The most common adverse eventwith candesartan 16 mg was dizziness, reported in 46 (30%) of 156 participants, compared with 19 (13%) of 151 in the placebo group.

坎地沙坦16 mg最常见的不良事件是头晕，156名参与者中有46人（30%）报告了这一症状，相比之下，安慰剂组的151名参与者中有19人（13%）报告了头晕。

Serious adverse events were reported in four (3%) participants in the candesartan 16 mg group and one (1%) participant in the placebo group.

在16毫克坎地沙坦组中有四名（3%）参与者报告了严重不良事件，在安慰剂组中有一名（1%）参与者报告了严重不良事件。

Adverse events leading to discontinuation occurred in four (3%) participants in both the candesartan 16 mg and placebo groups.

导致停药的不良事件在16毫克坎地沙坦组和安慰剂组中各有四名（各3%）参与者发生。

interpretation

Daily administration of candesartan 16 mg is effective and well tolerated as a preventive treatment for episodic migraine.

每日给予坎地沙坦16毫克作为偏头痛发作预防治疗是有效且耐受性良好的。

These findings support its role as a clinically meaningful and evidence-based option for migraine prevention.

这些发现支持其作为偏头痛预防的临床意义和循证医学选择。

However, further clinical trials and real-world data from registry studies are necessary to assess its long-term efficacy.

然而，需要进一步的临床试验和来自登记研究的真实世界数据来评估其长期疗效。

funding

Norwegian Research Council.

挪威研究委员会。