近日，英国南安普顿大学Paul White团队研究了克拉霉素与鼻内镜手术治疗成人慢性鼻窦炎伴和不伴鼻息肉（MACRO）的临床疗效。相关论文于2025年8月30日发表在《柳叶刀》杂志上。

由于缺乏关于鼻窦内窥镜手术和抗生素治疗慢性鼻窦炎的证据，导致鼻窦内窥镜手术率和抗生素使用差异达5倍。该研究旨在比较成人慢性鼻窦炎伴或不伴鼻息肉的鼻内窥镜手术或3个月克拉霉素治疗与鼻内药物治疗的临床疗效。

在这项实用的、三组、随机、安慰剂对照的4期试验中，参与者从英国的20个二级和三级医疗机构招募。慢性鼻窦炎成人（年龄≥18岁）在适当的药物治疗（鼻内皮质类固醇、生理盐水鼻冲洗和短期抗生素）后仍有症状，随机分配（1:1:1）接受鼻窦内镜手术（如果等待名单允许，在6周内随机化）加鼻内药物治疗，克拉霉素（250 mg每天两次，持续2周，然后250 mg每天一次，持续10周）加鼻内药物治疗。或者安慰剂加鼻内药物。鼻内用药包括鼻内皮质类固醇和生理盐水冲洗。参与者被分配到一个自动的、基于网络的安全随机化系统，在不同大小的排列块中（块大小为3和6），根据息肉和试验地点的存在进行分层。

参与者和现场小组不知道克拉霉素和安慰剂的分配，包括结局评估。主要结局指标是随机分组后6个月22项鼻结果测试（SNOT-22）生活质量问卷的总分，并进行意向治疗分析（ITT；可用病例基础）。评估了安全人群（克拉霉素和安慰剂）的不良反应，以及ITT人群（所有组）的严重不良事件。该试验已在ISRCTN注册中心（ISRCTN36962030）和EudraCT（2018-001100-11）注册，目前已完成，可选的长期随访正在进行中。

在2018年11月1日至2023年10月13日期间，研究组共招募了514名患有慢性鼻窦炎合并鼻息肉（n=410）或慢性鼻窦炎不合并鼻息肉（n=104）的参与者（181[35%]女性和333[65%]男性），并随机分配接受鼻窦内窥镜手术（n=171）、克拉霉素（n=172）或安慰剂（n=171），所有患者均接受鼻内药物治疗。随机分组后6个月，鼻窦内窥镜手术组的SNOT-22评分（经Bonferroni调整后的置信水平为98.33%）显著低于克拉霉素组（调整后的平均差值为- 18.13，p < 0001）和安慰剂组（- 20.44[- 26.42至- 14.46]，p < 0001）。6个月SNOT-22评分在随机分配给克拉霉素组和安慰剂组的参与者之间无显著差异（- 3.11[- 8.56至2.33]，p= 0.17）。9名受试者中发生了10个严重不良事件（172名受试者中2名（1%）发生了2个不良事件，171名受试者中3名（2%）发生了3个不良事件，171名受试者中4名（2%）发生了5个不良事件），没有一个是致命的。该研究不支持常规长期使用低剂量克拉霉素。如果单靠鼻内药物治疗无法控制症状，应建议进行鼻内窥镜鼻窦手术。

综上，MACRO试验表明，内镜鼻窦手术对慢性鼻窦炎患者具有临床效果，可显著提高6个月时疾病特异性生活质量。相反，试验结果不支持常规长期使用低剂量克拉霉素。如果单独使用鼻内药物无法控制症状，应建议进行鼻内镜手术。

附：英文原文

Title: The clinical effectiveness of clarithromycin versus endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps (MACRO): a pragmatic, multicentre, three-arm, randomised, placebo-controlled phase 4 trial

Author: Carl Philpott, David J Beard, Elnaz Saeedi, Jonathan A Cook, Stephen Jones, Caroline S Clarke, Lucinda Teoh, Mike Thomas, Paul Little, Jane Vennik, Valerie Lund, Anne G M Schilder, Fei Long, Stephen Durham, James Boardman, Claire Hopkins, Shazada Ahmed, Robert Almeyda, Rajiv Bhalla, Helen Blackshaw, Sean Carrie, Simon Gane, Richard Green, Iain Hathorn, Harsha Kariyawasam, Hisham Khalil, Matt Lechner, Paul Nix, Peter Prinsley, Yujay Ramakrishnan, Hesham Saleh, Rami Salib, Rishi Sharma, Sankalp Sunkaraneni, Irfan Syed, Neil Tan, Rishi Talwar, Paul White

Issue&Volume: 2025/08/30

Abstract:

Background

A paucity of evidence regarding use of endoscopic sinus surgery and antibiotics in managing chronic rhinosinusitis has contributed to a five-times variation in endoscopic sinus surgery rates, as well as variation in the use of antibiotics. The main aim of the present trial was to compare the clinical effectiveness of endoscopic sinus surgery or 3 months of clarithromycin treatment alongside intranasal medication in adults with chronic rhinosinusitis with or without nasal polyps.

Methods

In this pragmatic, three-arm, randomised, placebo-controlled phase 4 trial, participants were recruited from 20 secondary and tertiary care sites in the UK. Adults (aged ≥18 years) with chronic rhinosinusitis remaining symptomatic following appropriate medical therapy (intranasal corticosteroids, saline nasal irrigations, and a short course of antibiotics) were randomly assigned (1:1:1) to receive endoscopic sinus surgery (within 6 weeks of randomisation if waiting lists allowed) plus intranasal medication, clarithromycin (250 mg twice a day for 2 weeks then 250 mg once a day for 10 weeks) plus intranasal medication, or placebo plus intranasal medication. Intranasal medication comprised intranasal corticosteroids and saline irrigations. Participants were allocated with an automated, web-based secure randomisation system in permuted blocks of varying size (block sizes of three and six), stratified by the presence of polyps and trial site. Participants and site teams were masked to the clarithromycin and placebo allocations, including for outcome assessment. The primary outcome measure was the total score on the 22-item Sino-Nasal Outcome Test (SNOT-22) quality-of-life questionnaire at 6 months after randomisation, with analysis by intention to treat (ITT; available-case basis). Adverse reactions were assessed in the safety population (clarithromycin and placebo), and serious adverse events in the ITT population (all groups). The trial was registered on the ISRCTN registry, ISRCTN36962030, and EudraCT, 2018-001100-11, and is complete, with optional long-term follow-up ongoing.

Findings

Between Nov 1, 2018, and Oct 13, 2023, 514 participants (181 [35%] female and 333 [65%] male), with chronic rhinosinusitis with nasal polyps (n=410) or chronic rhinosinusitis without nasal polyps (n=104), were recruited and randomly assigned to receive endoscopic sinus surgery (n=171), clarithromycin (n=172), or placebo (n=171), all with intranasal medication. SNOT-22 scores at 6 months after randomisation were significantly lower (at the 98·33% confidence level after Bonferroni adjustment) in the endoscopic sinus surgery group than in the clarithromycin group (adjusted mean difference –18·13 [98·33% CI –24·26 to –11·99], p<0·0001) and placebo group (–20·44 [–26·42 to –14·46], p<0·0001). 6-month SNOT-22 scores did not differ significantly between participants randomly assigned to clarithromycin versus placebo (–3·11 [–8·56 to 2·33], p=0·17). Ten serious adverse events occurred in nine participants (two events in two [1%] of 172 participants allocated to clarithromycin, three events in three [2%] of 171 allocated to placebo, and five events in four [2%] of 171 allocated to endoscopic sinus surgery), none of which were fatal.

Interpretation

The MACRO trial shows that endoscopic sinus surgery has clinical effectiveness in patients with chronic rhinosinusitis, providing significantly improved disease-specific quality of life at 6 months. Conversely, the trial findings do not support routine long-term use of low-dose clarithromycin. Endoscopic sinus surgery should be recommended if intranasal medication alone is unable to achieve symptom control.

DOI: 10.1016/S0140-6736(25)01248-6

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01248-6/abstract