Positioning Second-line Therapies for Pneumocystis Jirovecii Pneumonia (PCP Alternatives)

Pneumocystis jirovecii pneumonia (PCP) is a serious lung infection that affects people with weakened immune systems (e.g., patients with cancer, organ transplants, autoimmune diseases, or HIV). Without timely treatment, PCP can lead to respiratory failure and death. TMP-SMX is the standard first-line treatment, but 20-30% of patients cannot receive the treatment or cannot tolerate it due to allergic reactions, kidney problems, low blood counts, drug interactions, or treatment failure. In these situations, doctors use alternative medications such as clindamycin with primaquine, pentamidine, or atovaquone. Although these alternative treatments are widely used, there is limited modern research directly comparing them. As a result, treatment choices vary between hospitals and physicians. The main objective of this study is to determine which alternative treatment works best for patients with PCP who cannot receive TMP-SMX. Eligible participants in the PCP alternatives therapy are enrolled and randomized centrally 1:1 in the MUHC Research Electronic Data Capture (REDCap) system. The primary outcome is a Hierarchical composite Win Ratio Outcome at day 30: death; new extracorporeal membrane oxygenation (ECMO), new invasive mechanical ventilation; severe (CTCAE grade 4) adverse drug event; and length of stay in hospital (amongst survivors). Secondary endpoints include individual components of the composite outcome, and tertiary endpoints include quality of life and longer-term outcomes through day 180.