Clarithromycin and endoscopic sinus surgery for adults with chronic rhinosinusitis with and without nasal polyps: Study protocol for the MACRO randomised controlled trial

Background: Chronic Rhinosinusitis (CRS) represents a common source of ill health; 11% of UK adults reported CRS symptoms in a worldwide population study. Guidelines are conflicting regarding whether antibiotics should be included in primary medical management, reflecting the lack of evidence seen from systematic reviews. Insufficient evidence to define the role of surgery contributes to a 5-fold variation in UK intervention rates. The objective of this trial is to establish the comparative effectiveness of endoscopic sinus surgery (ESS) or a prolonged course of antibiotics (clarithromycin) in adult patients with CRS in terms of symptomatic improvement and costs to the National Health Service (NHS) compared with standard medical care (intranasal medication) and each other at six months.
Methods: A 3-arm parallel group trial will be conducted where patients who remain symptomatic after receiving appropriate medical therapy (either in primary or secondary care) will be randomised to receive either intranasal medication plus endoscopic sinus surgery, intranasal medication plus clarithromycin (250mg) or intranasal medication plus placebo. Intranasal medication (current standard medical care) is defined as intranasal corticosteroids (INCS) spray or drops and saline irrigations. The primary outcome measure is the disease-specific health related quality of life SNOT-22 questionnaire. The study sample size is 600. Principal analyses will be according to the randomised groups irrespective of compliance. The trial will be conducted through at least 16 secondary/tertiary care centres with an internal pilot at 6 sites for 6 months.
Discussion: The potential cardiovascular side-effects of macrolide antibiotics have been recently highlighted. The effectiveness of antibiotics will be established through the trial, reducing unnecessary usage and potential morbidity. With respect to ESS, if it is shown to be clinically and cost effective, the trial may encourage earlier intervention. In contrast, if shown to be ineffective, this should achieve significant reductions in surgery rates. The trial results will feed into the other components of the MACRO research programme to establish best practice for the management of adults with Chronic Rhinosinusitis (CRS) and design the ideal patient pathway across primary and secondary care.
Trial registration: ISRCTN no: 36962030 (17th October 2018)