Phase 4 Trial Demonstrates Superior Efficacy of Endoscopic Sinus Surgery Over Antibiotics for Chronic Rhinosinusitis

A landmark phase 4 clinical trial has provided definitive evidence that endoscopic sinus surgery significantly outperforms long-term antibiotic therapy in treating chronic rhinosinusitis (搜索)搜索该疾病, a condition affecting one in 10 UK adults. The MACRO trial, involving 514 participants across 20 UK sites, demonstrated that surgical intervention delivers superior symptom relief and quality of life improvements compared to a three-month course of clarithromycin查看药品详情.

Trial Design and Patient Population

The MACRO study was a pragmatic, three-arm, randomized, placebo-controlled phase 4 trial conducted between November 2018 and October 2023. Researchers recruited 514 participants aged 18 years and older (65% male) with chronic rhinosinusitis (搜索)搜索该疾病 from secondary and tertiary care sites across the UK. The patient population included 410 individuals with nasal polyps and 104 without polyps, all of whom remained symptomatic despite standard treatment with intranasal corticosteroids, saline nasal irrigations, and short courses of antibiotics.

Participants were randomized 1:1:1 to receive endoscopic sinus surgery (within 6 weeks of randomization, n=171), clarithromycin查看药品详情 (250 mg twice daily for 2 weeks, then 250 mg once daily for 10 weeks, n=172), or placebo (n=171). All participants continued intranasal medication comprising corticosteroids and saline irrigations as standard care.

Primary Outcomes Show Clear Surgical Advantage

The primary endpoint measured total scores on the 22-item Sino-Nasal Outcome Test (SNOT-22) quality-of-life questionnaire at 6 months post-randomization using intention-to-treat analysis. Results demonstrated that participants receiving endoscopic sinus surgery achieved significantly lower SNOT-22 scores compared to both clarithromycin查看药品详情 (adjusted mean difference -18.13; 98.33% CI, -24.26 to -11.99; P <0.0001) and placebo groups (-20.44; 98.33% CI, -26.42 to -14.46; P <0.0001).

Notably, SNOT-22 scores showed no significant difference between clarithromycin查看药品详情 and placebo groups (-3.11; 98.33% CI, -8.56 to 2.33; P = 0.17), indicating that the antibiotic provided no meaningful benefit over placebo treatment. Among surgical patients, 87% reported improved quality of life at the six-month follow-up.

Safety Profile and Adverse Events

The trial identified 10 serious adverse events across 9 participants: 2 events in 2 clarithromycin查看药品详情 patients, 3 events in 3 placebo patients, and 5 events in 4 surgical patients. No events were fatal, suggesting acceptable safety profiles across all treatment arms.

Clinical Implications and Practice Changes

Lead investigator Carl Philpott from Norwich Medical School (搜索)搜索该词条 at the University of East Anglia查看公司主页 emphasized the clinical significance: "General practitioners and ear, nose, and throat specialists should be aware of the implications of the present findings for patients with chronic rhinosinusitis (搜索)搜索该疾病 who they see and treat. Patients could be advised of the high potential to benefit from endoscopic sinus surgery in terms of symptom relief when being counselled about how to manage their chronic rhinosinusitis."

The findings address a significant evidence gap that has led to wide practice variations, with clinicians performing endoscopic sinus surgery up to five times more often than prescribing antibiotics, despite limited supporting evidence. Previous randomized controlled trials examining longer-term antibiotic use had produced conflicting results, with a 2006 trial supporting macrolide therapy while a 2011 study found no significant benefit from azithromycin查看药品详情 over placebo.

Healthcare System Impact

Study co-author Professor Claire Hopkins from Guy's Hospital noted that uncertainty regarding surgical effectiveness had led to restricted NHS access for many patients. "The results of the MACRO trial highlight the significant improvements in quality of life that many patients experience after surgery, and should give them and their referring primary care doctors more confidence in seeking treatment for chronic rhinosinusitis (搜索)搜索该疾病," Hopkins stated.

The investigators concluded that implementing these findings in clinical care pathways could reduce unnecessary antibiotic prescriptions and decrease wait times for patients seeking surgical intervention, potentially generating cost savings through reduced consultations and prescriptions.

Ongoing Research

Researchers are continuing to assess the cost-effectiveness of sinus surgery while following trial participants over extended periods to determine the durability of treatment benefits. The collaborative MACRO programme involves researchers from University College London查看公司主页, University of East Anglia查看公司主页, Guy's and St Thomas' NHS Foundation Trust查看公司主页, University of Southampton, University of Oxford, UCLH, and Imperial College London, funded by the National Institute for Health and Care Research (搜索)搜索该词条.