Defining Antibiotic Treatment Duration for Ventilator - Associated Lung Infection
Status:
Recruiting
Trial end date:
2022-10-01
Target enrollment:
Participant gender:
Summary
Intensive care units (ICUs), with high antibiotic consumption, are epicentres of
antimicrobial resistance (AMR). Ventilator associated pneumonia (VAP) is the commonest
hospital-acquired infection (HAI) in ICUs and is associated with a high morbidity and
mortality in these vulnerable patients despite antibiotic therapy. No well-designed clinical
trials studying antibiotic duration for VAP caused by predominantly non-fermenting
Gram-negative bacteria have been conducted to date. Shortening antibiotic duration has the
potential to improve individual patient outcomes and indirectly benefit other patients by
reducing the selection pressure for multidrug resistant (MDR) bacteria within the ICU.
The study aims to demonstrate clinical non-inferiority-superiority of a short duration of
antibiotics (up to 7 days) versus prolonged antibiotic therapy (as per physician preference)
in adults with VAP in Asia. Patients who have been ventilated for more than 48 hours will be
screened daily for signs and symptoms of VAP according to the US Centers for Disease Control
and Prevention VAP criteria. Recruited patients will be reviewed daily for clinical signs of
stability including temperature <38°C for 48 hours, systolic blood pressure >90mmHg without
inotropes. Recruited patients will be randomised once they fulfill these clinical criteria of
stability. In the intervention arm, antibiotics should be stopped within 7 days once the
above criteria are fulfilled. In the control arm, antibiotics should be at least 7 days with
the exact duration decided by the managing physicians.
The primary outcome of the study is a combined endpoint of mortality and VAP recurrence at
day 60 of recruitment. The study hypothesis is that a shorter duration of treatment for VAP
(7 days or less depending on clinical response) is not only noninferior, but may also be
superior to a longer duration (8 days or more). The secondary outcomes of the study include
clinical parameters such as rate of acquisition of MDRO hospital-acquired infections,
duration of ventilation and hospitalization and days of antibiotics use. The study team will
also characterise the microbiome changes in study participants according to the type and
duration of antibiotics. MDROs collected will undergo whole genome sequencing for
transmission dynamics study. The study is a multinational multicenter study involving
hospitals in Asia.
Phase:
Phase 3
Details
Lead Sponsor:
University of Oxford
Collaborators:
Department for International Development, United Kingdom Mahidol Oxford Tropical Medicine Research Unit Medical Research Council