A Double-Blind, Randomised, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable COPD.


Allinson, James P, Vlies, Ben H, Brill, Simon E, Law, Martin, Burnside, Girvan ORCID: 0000-0001-7398-1346, Finney, Lydia J, Alves-Moreira, Luana, Donaldson, Gavin C, Calverley, Peter MA, Walker, Paul P ORCID: 0000-0002-5449-9551 et al (show 1 more authors) (2023) A Double-Blind, Randomised, Placebo-controlled Trial of Long-Term Doxycycline Therapy on Exacerbation Rate in Patients with Stable COPD. American journal of respiratory and critical care medicine, 208 (5). pp. 549-558.

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Abstract

<h4>Rationale</h4>COPD exacerbations are a major cause of morbidity and mortality and preventing them is a key treatment target. Long-term macrolide treatment is effective at reducing exacerbations but there is a paucity of evidence for other antibiotic classes. To assess whether 12-month use of doxycycline reduces exacerbation rate in people with COPD.<h4>Methods</h4>People with moderate to very severe COPD and an exacerbation history were recruited from 3 UK centres and randomised to 12-months doxycycline 100mg once daily or placebo. The primary study outcome was exacerbation rate per person year.<h4>Results</h4>222 people were randomised. Baseline mean FEV1 was 1.35 (SD 0.35) L; 52.5 (SD 15.9) % predicted. Median number of treated exacerbations in the year before the study was 2 (1-4). 71% of patients reported ≥2 exacerbations. 81% were already prescribed inhaled corticosteroids at baseline. COPD exacerbation rate did not differ between the groups - doxycycline/placebo rate ratio 0.86 (0.67, 1.10); p=0.23. No difference was seen if only treated exacerbations or hospitalisations were considered. In pre-planned sub-group analysis, doxycycline appeared to better reduce the exacerbation rate among people with severe COPD (RR:0.36 (0.15, 0.85); p=0.019), and in those with an eosinophil count <300 cells/μL (RR:0.50 (0.29, 0.84); p=0.01). Health status measured by SGRQ was 5.2 points worse in the doxycycline group at 12-months (p<0.007).<h4>Conclusions</h4>Doxycycline did not significantly reduce exacerbation rate, over 12-months, in participants with COPD, who exacerbated regularly, but may have benefitted those with more severe COPD or blood eosinophil counts <300 cells/μL. Clinical trial registration available at www.<h4>Clinicaltrials</h4>gov, ID: NCT02305940.

Item Type: Article
Uncontrolled Keywords: chronic obstructive pulmonary disease, exacerbations, long-term, antibiotic, clinical trial
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Population Health
Depositing User: Symplectic Admin
Date Deposited: 30 Aug 2023 08:35
Last Modified: 18 Oct 2023 16:38
DOI: 10.1164/rccm.202212-2287oc
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3172399
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