基层医疗中偏头痛一线预防性治疗效果的比较：一项实用临床试验的研究方案（PREMI研究）

Comparison of the effectiveness of first-line preventive treatment of migraine in primary care: study protocol for a pragmatic clinical trial (PREMI study).

作者信息

Giner-Soriano Maria, Morros Rosa, Monfà Ramon, Ouchi Dan, Fernández-García Silvia, Vedia Cristina, Bonet Monné Sara, Calvo Martínez Eva María, Copetti Fanlo Silvia, Morollón Noemí, Belvís Nieto Robert, Delgado-Espinoza Claudia Erika, García-Sangenís Ana

机构信息

Fundació Institut Universitari per a La Recerca a L'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Gran Via de Les Corts Catalanes 587, Àtic, 08007, Barcelona, Spain.

Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Spain.

出版信息

Trials. 2025 Aug 26;26(1):311. doi: 10.1186/s13063-025-08961-0.

DOI:10.1186/s13063-025-08961-0

PMID:40859286

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12382017/

Abstract

BACKGROUND

Migraine is a neurological disorder affecting approximately 12% of the population, more frequent in women, causing disability. Preventive treatment is recommended to prevent chronification and analgesics' abuse and to improve quality of life, but not all candidates receive it. Common preventive drugs include amitriptyline, flunarizine, propranolol, and topiramate. Their effectiveness and safety have not yet been assessed in our setting. The objective of this study is to evaluate the effectiveness of these drugs in reducing the monthly migraine days (MMD) and to evaluate their safety.

METHODS

Phase IV, pragmatic randomized clinical trial of four parallel groups, open and multicentric, in Primary Care in Catalonia, Spain. We will include adults with migraine eligible for preventive treatment. They will be randomized to the following: (1) propranolol, (2) amitriptyline, (3) flunarizine, or (4) topiramate. The main efficacy measure will be the change in the mean MMD at week 12 in comparison to the mean MMD at baseline. Other secondary efficacy and safety measures will be assessed. The main non-inferiority analysis will be conducted in the per protocol population at week 12, comparing topiramate versus propranolol as the main analysis, and amitriptyline and flunarizine versus propranolol as exploratory analyses.

DISCUSSION

There are epidemiological, clinical and pharmacological sex-differences in migraine which may result in differences in the use of migraine preventive drugs. However, the effectiveness of the most frequent preventive treatment and the differences in effectiveness and safety between women and men have not yet been studied. Moreover, as new expensive drugs have been authorized for preventive treatment, indicated when the usual drugs have failed, assessing the effectiveness and safety of the usual oral preventive drugs through a clinical trial is especially important. We also plan to evaluate their cost-effectiveness, and the clinical trial will count on an active contribution from patients through an app designed for this purpose, which may help in the management of the disease in the future.

TRIAL REGISTRATION

ClinicalTrials.gov ID: NCT06499116 ( https://clinicaltrials.gov/study/NCT06499116 ). Trial registration date: July 12, 2024. EU CT Number: 2024-513597-22. Protocol ID: IJG-PREMI-2024.

SPONSOR

Fundació d'Investigació en Atenció Primària Jordi Gol i Gurina. Gran Via de les Corts Catalanes 587, àtic. 08007, Barcelona, Spain.

摘要

背景

偏头痛是一种影响约12%人口的神经系统疾病，在女性中更为常见，会导致残疾。推荐进行预防性治疗以防止病情慢性化和止痛药滥用，并改善生活质量，但并非所有符合条件的患者都接受该治疗。常见的预防性药物包括阿米替林、氟桂利嗪、普萘洛尔和托吡酯。在我们的研究环境中，它们的有效性和安全性尚未得到评估。本研究的目的是评估这些药物在减少每月偏头痛天数（MMD）方面的有效性，并评估其安全性。

方法

在西班牙加泰罗尼亚的初级保健机构进行的一项四平行组、开放、多中心的IV期实用随机临床试验。我们将纳入有资格接受预防性治疗的偏头痛成年患者。他们将被随机分为以下几组：（1）普萘洛尔，（2）阿米替林，（3）氟桂利嗪，或（4）托吡酯。主要疗效指标将是第12周时平均MMD与基线时平均MMD的变化。还将评估其他次要疗效和安全性指标。主要的非劣效性分析将在第12周的符合方案人群中进行，将托吡酯与普萘洛尔作为主要分析进行比较，将阿米替林和氟桂利嗪与普萘洛尔作为探索性分析进行比较。

讨论

偏头痛在流行病学、临床和药理学方面存在性别差异，这可能导致偏头痛预防性药物使用的差异。然而，最常用的预防性治疗的有效性以及男女之间有效性和安全性的差异尚未得到研究。此外，由于新的昂贵药物已被批准用于预防性治疗，适用于常规药物治疗失败的情况，通过临床试验评估常规口服预防性药物的有效性和安全性尤为重要。我们还计划评估它们的成本效益，并且该临床试验将通过为此目的设计的应用程序获得患者的积极参与，这可能有助于未来的疾病管理。