Reducing antibiotic treatment duration for ventilator-associated pneumonia (REGARD-VAP): a trial protocol for a randomised clinical trial

Abstract

IntroductionVentilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICUs). Using short-course antibiotics to treat VAP caused by Gram-negative non-fermenting bacteria has been reported to be associated with excess pneumonia recurrences. The “REducinG Antibiotic tReatment Duration for Ventilator-Associated Pneumonia” (REGARD-VAP) trial aims to provide evidence for using a set of reproducible clinical criteria to shorten antibiotic duration for individualised treatment duration of VAP.Methods and analysisThis is a randomised controlled hierarchical non-inferiority–superiority trial being conducted in ICUs across Nepal, Thailand and Singapore. The primary outcome is a composite endpoint of death and pneumonia recurrence at day 60. Secondary outcomes include ventilator-associated events, multidrug-resistant organism infection or colonisation, total duration of antibiotic exposure, mechanical ventilation and hospitalisation. Adult patients who satisfy the US Centers for Disease Control and Prevention National Healthcare Safety Network VAP diagnostic criteria are enrolled. Participants are assessed daily until fever subsides for >48 hours and have stable blood pressure, then randomised to a short duration treatment strategy or a standard-of-care duration arm. Antibiotics may be stopped as early as day 3 if respiratory cultures are negative, and day 5 if respiratory cultures are positive in the short-course arm. Participants receiving standard-of-care will receive antibiotics for at least 8 days. Study participants are followed for 60 days after enrolment. An estimated 460 patients will be required to achieve 80% power to determine non-inferiority with a margin of 12%. All outcomes are compared by absolute risk differences. The conclusion of non-inferiority, and subsequently superiority, will be based on unadjusted and adjusted analyses in both the intention-to-treat and per-protocol populations.Ethics and disseminationThe study has received approvals from the Oxford Tropical Research Ethics Committee and the respective study sites. Results will be disseminated to patients, their caregivers, physicians, the funders, the critical care societies and other researchers.Trial registration numberNCT03382548.

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“…The introduction of fast molecular microbiology tests has overturned the concepts of empirical therapy/targeted therapy. Moreover, an ongoing trend to avoid excessive and possibly unnecessary durations of antibiotic therapies can be observed [46][47][48].…”

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“…The 2017 European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines and the 2016 IDSA guidelines [ 232 ] both recommend 7 days of therapy for HAP/VAP. Ongoing studies [ 233 ] are determining if therapy duration could be reduced further.…”

Ten golden rules for optimal antibiotic use in hospitals: based on the publication statement of the International Network Group of the World Antimicrobial Resistance

“…The Ukrainian Journal of Clinical Surgery 2016 IDSA guidelines [232] recommend 7 days of therapy for CAP/VAP. An ongoing study [233] will determine whether the duration of therapy can be further reduced.…”