Multicentre open-label randomised controlled trial to evaluate the efficacy and safety of moderate-dose and high-dose intravenous methylprednisolone combined with plasmapheresis versus plasmapheresis alone in leptospirosis pulmonary haemorrhage syndrome: a protocol.

Leptospirosis is a zoonotic infection caused by the bacterium Leptospira, which typically enters humans through contact with water or soil contaminated with infected urine. One of the most important causes of death due to leptospirosis is leptospirosis pulmonary haemorrhage syndrome (LPHS). LPHS occurs due to an inappropriate immune response, resulting in excessive release of cytokines/chemokines or direct damage to alveoli by bacteria. Mortality remains high in LPHS, and management strategies of this deadly complication are under-investigated. Survivors have minimal residual lung injury, necessitating evidence-based treatment to improve mortality in LPHS. Steroids and plasmapheresis have been tried in many case series but lack robust evidence. Plasmapheresis has become a standard practice in Sri Lanka for managing LPHS, guided by expert opinion. This study will try to determine the effect of moderate-dose or high-dose steroid combination with plasmapheresis compared with plasmapheresis alone as a treatment for LPHS. This open-label, randomised controlled trial will enrol LPHS patients from four selected tertiary care hospitals in Sri Lanka. Participants will be randomly assigned to three groups in a 1:1:1 ratio to receive plasmapheresis alone, plasmapheresis with 150 mg/day methylprednisolone for 3 days or plasmapheresis with 1000 mg/day methylprednisolone for 3 days. Recruitment will consist of 28 participants to each arm of the trial. Diagnosis will be confirmed by Leptospira-specific PCR and microscopic agglutination test. Analysis will follow intention-to-treat principles with adjustment for multiple comparisons. Primary outcome is all-cause mortality at 28 days. Secondary outcomes include hospital-acquired infections, duration of respiratory support, duration of intensive care unit stay, duration of hospital stay and side effects of steroid therapy. The ethical approval was obtained from the Research Ethics Committee of the University of Sri Jayewardenepura (ERC 20/24) and the trial has been registered in the Sri Lanka Clinical Trials Registry (SLCTR/2024/037). Trial is approved by the National Medicines Regulatory Authority in Sri Lanka (NMRA/CTRD/PA4/54). Study findings will be disseminated through peer-reviewed publications and conference presentations. Sri Lanka Clinical Trials Registry, Number SLCTR/2024/037.