Dataset Information

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

ABSTRACT:

Background

Chronic rhinosinusitis (CRS) is 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 in systematic reviews. Insufficient evidence to inform the role of surgery contributes to a fivefold 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 compared with standard medical care (intranasal medication) at 6 months.

Methods/design

A three-arm parallel-group trial will be conducted with patients who remain symptomatic after receiving appropriate medical therapy (either in primary or secondary care). They will be randomised to receive: (1) intranasal medication plus ESS, (2) intranasal medication plus clarithromycin (250?mg) or (3) intranasal medication plus a placebo. Intranasal medication (current standard medical care) is defined as a spray or drops of intranasal corticosteroids and saline irrigations. The primary outcome measure is the SNOT-22 questionnaire, which assesses disease-specific health-related quality of life. The study sample size is 600. Principal analyses will be according to the randomised groups irrespective of compliance. The trial will be conducted in at least 16 secondary or tertiary care centres with an internal pilot at six 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 this trial, which may help to reduce unnecessary usage and potential morbidity. If ESS is shown to be clinically effective and cost-effective, the trial may encourage earlier intervention. In contrast, if it is shown to be ineffective, then there should be a significant reduction 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 CRS and design the ideal patient pathway across primary and secondary care.

Trial registration

ISRCTN36962030 . Registered on 17 October 2018.

SUBMITTER: Philpott C

PROVIDER: S-EPMC6489242 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Philpott Carl C le Conte Steffi S Beard David D Cook Jonathan J Sones William W Morris Steve S Clarke Caroline S CS Thomas Mike M Little Paul P Vennik Jane J Lund Valerie V Blackshaw Helen H Schilder Anne A Durham Stephen S Denaxas Spiros S Carpenter James J Boardman James J Hopkins Claire C

Trials 20190429 1

<h4>Background</h4>Chronic rhinosinusitis (CRS) is 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 in systematic reviews. Insufficient evidence to inform the role of surgery contributes to a fivefold variation in UK intervention rates. The objective of this trial is to establish the comparative effectiven ...[more]

PMID: 31036048

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Project description:ImportanceAlthough oral corticosteroids are commonly prescribed following endoscopic sinus surgery (ESS) for chronic rhinosinusitis (CRS) without nasal polyposis, there are little data to suggest that this is a beneficial practice.ObjectiveTo assess the efficacy of oral corticosteroids following ESS in CRS without polyps.Design, setting, and participantsThis prospective double-blinded, placebo-controlled, randomized noninferiority clinical trial conducted in a single academic tertiary rhinology practice included adults with CRS without polyps undergoing ESS. Of 81 patients recruited, 72 completed the study.InterventionsPatients were randomized into 2 treatment groups: a 12-day postoperative taper of oral prednisone vs matched placebo tablets. All study patients also received a uniform 2-week postoperative regimen of oral antibiotics, fluticasone nasal spray, and saline rinses.Main outcomes and measuresThe primary outcome measures were Sinonasal Outcome Test-22 (SNOT-22) scores and Lund-Kennedy endoscopy scores, collected preoperatively and postoperatively at 1 week, 1 month, 3 months, and 6 months. Scores were compared between treatment groups at each time point using longitudinal difference between treatment groups and analyzed using 2-way, repeated measures analysis of variance. Secondary outcome measures included treatment-related adverse effects.ResultsOverall, 72 patients (mean [SD] age, 49.4 [14.9] years; 36 men, 36 women) completed the study, with 33 in the prednisone arm and 39 in the placebo arm. When comparing longitudinal differences between treatment groups, there was no clinically meaningful difference observed in SNOT-22 total (F[4254] = 1.71, η2 = 0.01 [95% CI, 0.00-0.05]) or Lund-Kennedy scores (F[4247] = 1.23, η2 = 0.02 [95% CI, 0.00-0.50]). In SNOT-22 subdomain analyses, there was no clinically meaningful difference between treatment groups for rhinologic, extranasal rhinologic, ear/facial, or sleep subdomains. However, the prednisone group had worse longitudinal scores for psychological dysfunction compared with the placebo group (F[4254] = 3.18, η2 = 0.05 [95% CI, 0.02-0.09]). Reported adverse effects were similar between the 2 treatment groups.Conclusions and relevanceIn this randomized clinical trial of patients with CRS without polyps, oral prednisone following ESS conferred no additional benefit over placebo in terms of SNOT-22 total scores, SNOT-22 rhinologic subscores, or Lund-Kennedy endoscopy scores up to 6 months after surgery. Patients receiving prednisone, however, did demonstrate worse SNOT-22 psychologic subdomain scores. These results suggest that the risks of oral corticosteroids may outweigh the benefits; thus use of oral corticosteroids after ESS for CRS without polyps should be carefully considered.Trial registrationClinicalTrials.gov Identifier: NCT02748070.

Project description:BackgroundComparative effectiveness research between endoscopic sinus surgery (ESS) and biologic therapy for severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a nascent field as new therapeutic modalities become clinically available.MethodsA prospective, multicenter cohort of CRSwNP patients, undergoing ESS between 2011 and 2019, were compared to phase-3 biologic trial data. Patients undergoing ESS received baseline nasal endoscopy quantified via Lund-Kennedy (LK) grading. Patients meeting inclusion criteria, modified from Dupilumab-LIBERTY-NP-24&52, omalizumab-POLYP-1&2, and Mepolizumab-SYNAPSE clinical trials, were included in this study. Baseline characteristics and outcome measures were compared between these cohorts at 24 weeks and 52 weeks, when possible.ResultsA total of 111 CRSwNP patients met modified inclusion criteria. There were no statistically significant differences in baseline age, sex, asthma status, aspirin-exacerbated respiratory disease status, smell identification, LK-polyp score, and Lund-Mackay computed tomography (CT) scores between ESS and biologic groups. At 24 weeks, ESS demonstrated significantly greater improvements in 22-item Sino-Nasal Outcome Test (SNOT-22) compared to one (of two) dupilumab trials (p < 0.05) and both omalizumab trials (p < 0.001). ESS associated with significantly lower nasal polyp scores (NPS) compared to dupilumab (p < 0.001) and omalizumab (p < 0.001), despite comparable improvements in smell identification (p > 0.05). At 52 weeks, ESS resulted in statistically similar improvement in SNOT-22 scores compared to dupilumab (p = 0.21), but NPS remained significantly lower in the ESS group compared to dupilumab (p < 0.001) and mepolizumab (p < 0.001).ConclusionAt 24 weeks and 52 weeks, ESS offers comparable SNOT-22 improvements compared to dupilumab. ESS and dupilumab offer comparable improvement in smell identification at 24 weeks. Compared to omalizumab, ESS offers superior SNOT-22 improvements. ESS offers significantly greater reductions in polyp size compared to omalizumab, dupilumab, and mepolizumab therapies.

Dataset Information

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

Background

Methods/design

Discussion

Trial registration

Publications

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

Similar Datasets

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