NCT07357103

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

Positioning Second-line Therapies for Pneumocystis Jirovecii Pneumonia (PCP Alternatives) [A Branch of the Initial Treatment Domain of the SPIRIT-PCP Platform]

• Status: Not Yet Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 416 (estimated)
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The usual first treatment for Pneumocystis jirovecii pneumonia (PCP) is an antibiotic called trimethoprim-sulfamethoxazole (TMP-SMX). However, some patients cannot take this medication because of allergies, side effects, or lack of response. This study asks the question: When TMP-SMX cannot be used, which alternative treatment for PCP provides the best balance of effectiveness and safety?

Detailed description

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.

Conditions

• Pneumocystis
• Pneumocystis Infection
• Pneumocystis Carinii Infection
• Pneumocystis Carinii; Infection, Resulting From HIV Disease
• Pneumocystis Jirovecii Pneumonia
• Pneumocystis Jirovecii Infection
• Pneumocystosis Associated With AIDS
• Pneumocystosis; Pneumonia (Etiology)

Interventions

Type	Name	Description
DRUG	Clindamycin + primaquine	Participants randomized to this intervention will receive clindamycin in combination with primaquine as second-line therapy for the treatment of PCP. This regimen may be used for participants with Severe PCP or mild to moderate PCP in acccordance with protocol-defined disease severity and standard clinical practice.
DRUG	Pentamidine	Participants randomized to this intervention will receive pentamidine, administered intravenously, as second-line therapy for the treatment of PCP in patients with severe disease who are unable to tolerate or have contraindications to trimethoprim-sulfamethoxazole (TMP/SMX)
DRUG	Atovaquone	Participants randomized to. this intervention will receive atovaquone, administered orally, as second-line therapy for the treatment of PCP in participants with mild to moderate disease who are unable to tolerate or have contraindications to trimethoprim-sulfamethozaxole (TMP/SMX).

Timeline

• Start date: 2026-03-01
• Primary completion: 2029-03-01
• Completion: 2029-09-01
• First posted: 2026-01-21
• Last updated: 2026-01-21