采用厄多司坦和/或阿奇霉素治疗原发性纤毛运动障碍患儿和成人减少恶化（REPEAT 试验）：一项多中心、双盲、双模拟、2×2 部分析因、随机对照试验的研究方案。

Reducing exacerbations in children and adults with primary ciliary dyskinesia using erdosteine and/or azithromycin therapy (REPEAT trial): study protocol for a multicentre, double-blind, double-dummy, 2×2 partial factorial, randomised controlled trial.

机构信息

Child Health Division and NHMRC Centre for Research Excellence in Paediatric Bronchiectasis (AusBREATHE), Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory, Australia

Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.

出版信息

BMJ Open Respir Res. 2022 May;9(1). doi: 10.1136/bmjresp-2022-001236.

DOI:10.1136/bmjresp-2022-001236

PMID:35534039

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9086630/

Abstract

INTRODUCTION

Primary ciliary dyskinesia (PCD) is a rare, progressive, inherited ciliopathic disorder, which is incurable and frequently complicated by the development of bronchiectasis. There are few randomised controlled trials (RCTs) involving children and adults with PCD and thus evidence of efficacy for interventions are usually extrapolated from people with cystic fibrosis. Our planned RCT seeks to address some of these unmet needs by employing a currently prescribed (but unapproved for long-term use in PCD) macrolide antibiotic (azithromycin) and a novel mucolytic agent (erdosteine). The primary aim of our RCT is to determine whether regular oral azithromycin and erdosteine over a 12-month period reduces acute respiratory exacerbations among children and adults with PCD. Our primary hypothesis is that: people with PCD who regularly use oral azithromycin and/or erdosteine will have fewer exacerbations than those receiving the corresponding placebo medications. Our secondary aims are to determine the effect of the trial medications on PCD-specific quality-of-life (QoL) and other clinical outcomes (lung function, time-to-next exacerbation, hospitalisations) and nasopharyngeal bacterial carriage and antimicrobial resistance.

METHODS AND ANALYSIS

We are currently undertaking a multicentre, double-blind, double-dummy RCT to evaluate whether 12 months of azithromycin and/or erdosteine is beneficial for children and adults with PCD. We plan to recruit 104 children and adults with PCD to a parallel, 2×2 partial factorial superiority RCT at five sites across Australia. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, lung function and nasopharyngeal carriage by respiratory bacterial pathogens and their associated azithromycin resistance.

ETHICS AND DISSEMINATION

Our RCT is conducted in accordance with Good Clinical Practice and the Australian legislation and National Health and Medical Research Council guidelines for ethical conduct of Research, including that for First Nations Australians.

TRIAL REGISTRATION NUMBER

ACTRN12619000564156.

摘要

介绍

原发性纤毛运动障碍（PCD）是一种罕见的、进行性的、遗传性的纤毛病，无法治愈，常并发支气管扩张。目前仅有少数涉及儿童和成人 PCD 的随机对照试验（RCT），因此干预措施的疗效证据通常是从囊性纤维化患者中推断出来的。我们计划的 RCT 通过使用目前规定的（但未批准长期用于 PCD）大环内酯类抗生素（阿奇霉素）和新型黏液溶解剂（厄多司坦）来解决其中一些未满足的需求。我们的 RCT 的主要目的是确定在 12 个月的时间内，定期口服阿奇霉素和厄多司坦是否能减少 PCD 儿童和成人的急性呼吸道恶化。我们的主要假设是：定期使用口服阿奇霉素和/或厄多司坦的 PCD 患者的恶化次数将少于接受相应安慰剂药物的患者。我们的次要目标是确定试验药物对 PCD 特定生活质量（QoL）和其他临床结果（肺功能、下一次恶化时间、住院）以及鼻咽细菌携带和抗菌药物耐药性的影响。

方法和分析

我们目前正在进行一项多中心、双盲、双模拟 RCT，以评估 12 个月的阿奇霉素和/或厄多司坦是否对 PCD 儿童和成人有益。我们计划在澳大利亚五个地点招募 104 名 PCD 儿童和成人参加平行、2×2 部分因子优效性 RCT。我们的主要终点是 12 个月内恶化的发生率。我们的主要次要结果是 QoL、肺功能以及鼻咽呼吸病原体携带及其相关的阿奇霉素耐药性。