British experts have suggested, after a recent study, that surgery – not antibiotics – might be the best way to treat chronic rhinosinusitis, which leaves people with a permanently blocked or runny nose and a reduced sense of smell.
Although surgery is typically a last resort for people with a chronically blocked or runny nose, in some cases it may actually work better than the antibiotics that are routinely prescribed to treat the condition, reports New Scientist.
Chronic sinusitis affects about 9% of people worldwide and occurs when the mucus-producing cavities – sinuses – around the nose become inflamed. Common symptoms include a blocked or runny nose, a reduced sense of smell and facial pain, with these persisting for more than 12 weeks. The cause of the condition is usually unclear but may involve viral infections or a change to the nose microbiome.
The first line of treatment involves anti-inflammatory nasal sprays and flushing saline solution through the nose daily. But if symptoms persist, doctors often prescribe a three-month course of the antibiotic clarithromycin. This is used for its anti-inflammatory properties rather than its bacteria-killing properties, says Carl Philpott at the University of East Anglia in the United Kingdom.
As a last resort, people can undergo surgery to widen the sinuses and remove any benign nasal growths, or polyps, which form and worsen symptoms in about 5% of cases. Yet no prior study has directly compared surgery with antibiotics.
To fill this gap, Philpott and his colleagues recruited more than 500 adults with chronic rhinosinusitis. In surveys, the participants rated the severity of 22 symptoms, such as facial pain and how runny their nose was, with an average score of 55 out of 110.
The team then randomly assigned the participants to take either a three-month course of clarithromycin, placebo pills or undergo nasal surgery. All the participants also used nasal sprays and rinsed their noses with saline.
Six months later, those who took either clarithromycin or placebo pills reported a roughly 10-point reduction in the severity of their symptoms compared with before the treatment, a level that would noticeably improve their quality of life, said team member Claire Hopkins at King’s College London. But since the effect was seen in both the antibiotic and placebo groups, it was probably due to the nasal sprays and rinsing, she said.
Those in the surgery group saw a roughly 30-point improvement in their symptoms compared with before surgery, suggesting doctors should offer this instead of antibiotics, wrote the authors in their paper, published in The Lancet.
There is an important caveat, however. About 80% of the participants had nasal polyps, possibly because the study took place during the Covid-19 pandemic, and catching the coronavirus may trigger the kind of inflammation that leads to polyps, said Hopkins.
Further studies are needed to check whether the results apply to those without polyps, who we know harbour different types of inflammation, she added.
Study details
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
Carl Philpott, David Beard, Elnaz Saeedi, et al
Published in The Lancet on 30 August 2025
Summary
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 three 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.
The Lancet article – 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 (Open access)
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01248-6/fulltext
New Scientist article – Go-to therapy for chronic sinus condition doesn't work that well (Open access)
https://www.newscientist.com/article/2494299-go-to-therapy-for-chronic-sinus-condition-doesnt-work-that-well/
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