Effect of maintenance macrolide antibiotics withdrawal in obstructive airway diseases

ABSTRACT

Introduction/Aim: While effective and recommended, concerns remain over the widespread, long-term use of macrolide antibiotics in obstructive airway diseases (OADs), particularly relating to antimicrobial resistance. The main objective of this study is to evaluate the effect of deescalation of maintenance macrolide antibiotics during the Australian summer season on exacerbations of OADs. Methods: A double-blind, placebo-controlled, non-inferiority, randomized-controlled trial designed using telehealth. All assessments are conducted over the phone, and the allocated study medication is mailed to participants. We plan to recruit 160 adult participants who are on maintenance macrolide therapy for at least 6 months for the management of asthma, COPD or bronchiectasis. Participants will be randomized to two arms at the start of summer, arm-1 participants will switch from their current macrolide to azithromycin 500 mg for 9 months while arm-2 participants will switch to an identical placebo for the same duration. Telephone follow-up interviews will be conducted at 3-, 6- and 9-months with two additional safety check-in calls during the initial 3 months. The primary outcome is exacerbation. Results: The recruitment and follow-ups are ongoing, without interruption by the COVID-19 lockdowns. We have recruited 39 patients (mean age ± SD 70.0 ± 9.32;54% male) in 2020, and 28 (72%) successfully completed the 9-month treatment with allocated study medication. Of the remaining, 10 were discontinued due to worsening symptoms/exacerbations, and one due to a serious adverse event (SAE). The retention rate at 9-month is currently at 97%. A total of seven unrelated SAEs have been reported so far (all resolved). Conclusion: This novel study will allow us to determine the effect of treatment breaks during periods of lower exacerbation risk. The telehealth-based study design is COVID-19 appropriate and provided greater flexibility for participants to attend interviews, improving the recruitment and retention rate.