Journal Article

Role of Adjunctive corticoSTEROIDs on clinical outcomes in severe Scrub typhus pneumonitis: ASTEROIDS study protocol – a randomised controlled trial

Ray, Sumit, Krishna, Bhuvana, Chaudhry, Dhruva, Gunasekaran, Karthik, Varghese, George M, Venkatesh, Balasubramanian, Chacko, Binila, Chandiraseharan, Vignesh Kumar, Wyawahare, Mukta, Rathinam, Jasper, Saravu, Kavitha, Carey, Ronald, Premkumar, Prasanna S, Peter, John Victor

2025

Overview

IntroductionRecent studies have demonstrated a beneficial role of steroids in severe community-acquired pneumonia, severe COVID-19 infection and acute respiratory distress syndrome (ARDS) of diverse aetiology. This multicentre randomised controlled trial in severe scrub typhus pneumonitis and ARDS will compare the effects of 6 mg of dexamethasone once per day with placebo, in addition to standard treatment, on ventilator-free days (VFD), mortality and ventilatory requirement.Methods and analysisThe study, involving six sites, will recruit 440 patients with severe scrub typhus pneumonitis or ARDS to concealed, block-randomised, site-specific assignment of dexamethasone or placebo for 4–7 days. The primary outcome will be VFD, defined as days alive and free of ventilation at 28 days. Secondary outcomes will include 28-day mortality, need and duration of ventilation, and treatment failure, defined as death, or escalation of respiratory support from simple devices (nasal cannula, mask) to non-invasive or invasive ventilation, or the use of open-labelled steroids for worsening shock. The study will also ascertain if antinuclear antibody (ANA) expression during the acute phase of illness will predict steroid responsiveness. Subgroup analyses will be conducted a priori on ANA expression and the need for ventilation. All analyses will be conducted on an intention-to-treat basis. The trial, which commenced in April 2025, would clarify the role of corticosteroids in scrub typhus pneumonitis.Ethics and disseminationThe Institutional Review Board and Ethics Committee of the lead site, Christian Medical College, Vellore, India, has approved the study (IRB Min No 15920 (INTERVE) dated 22 November 2023). The remaining five sites have obtained approval from their respective ethics committees. Study results will be published in an international peer-reviewed journal.Trial registration numberCTRI/2024/12/077709. Registered 5 December 2024.

• Publisher: British Medical Journal Publishing Group,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adult intensive & critical care / Clinical Trial / COVID-19 / Dexamethasone - administration & dosage / Dexamethasone - therapeutic use / Diagnostic tests / Disease transmission / Drug Therapy / Fatalities / Glucocorticoids - therapeutic use / Humans / Illnesses / Infections / Intensive Care / Meta-analysis / Mortality / Multicenter Studies as Topic / Patients / Pneumonia / Pneumonia - drug therapy / Pneumonia - mortality / Protocol / Randomized Controlled Trials as Topic / Respiration, Artificial / Respiratory distress syndrome / Respiratory Distress Syndrome - drug therapy / Respiratory Distress Syndrome - mortality / Scrub Typhus - complications / Scrub Typhus - drug therapy / Scrub Typhus - mortality / Sepsis / Steroids / Systematic review / Treatment Outcome / Tropical medicine / Typhus / Ventilators / Ventilators, Mechanical