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

NCT07357103 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: 2026-12268527077
• Study Type: interventional
• Target: 416
• Locations: 0 countries
• Sites: N/A

Brief 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?

Conditions

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

Keywords

PCP; Pneumocystis jirovecii pneumonia; PCP Alternatives; Clindamycin; Pentamidine; Primaquine; Atovaquone; HIV; Non-HIV; Immunocompromised host; Randomized Control Trial

Outcome Measures

Primary Outcomes (1)

• Hierarchical composite outcome

  Hierarchical composite of Win Ratio at day 30: * death; * new extracorporeal membrane oxygenation (ECMO), * new invasive mechanical ventilation; * severe (CTCAE grade 4) adverse drug event (dermatologic, nephrologic, hematologic, neurologic, and/or endocrinologic) considered at least probable (by Leape and Bates criteria); * new non-invasive ventilation; * change of therapy (i.e., dose or agent) due to presumed treatment failure or probable adverse drug reaction (by Leape and Bates criteria); and * length of stay in hospital (amongst survivors)

  Day 30

Secondary Outcomes (7)

• Proportion of patients that die (death)

  Day 30

• Proportion of patients with a need for new extracorporeal membrane oxygenation (ECMO),

  Day 30

• Proportion of patients requiring new Invasive Mechanical Ventilation

  Day 30

• Proportion of patients with severe (CTCAE grade 4) adverse drug event

  Day 30

• Proportion of patients with need for new non-invasive ventilation;

  Day 30

Other Outcomes (4)

• Tertiary outcome measure of quality of life at day 30

  Day 30

• Tertiary outcome measure of all-cause mortality

  Day 180

• Tertiary Outcome Measure of PCP recurrence

  Day 180

Study Arms (4)

Severe PCP-Clindamycin+primaquine

EXPERIMENTAL

Participants with severe PCP will be randomized to receive clindamycin in combination with primaquine as second-line therapy due to intolerance of or contraindications to trimethoprim-sulfamethoxazole.

Drug: Clindamycin + primaquine

Severe PCP-Intravenous Pentamidine

EXPERIMENTAL

Participants with severe PCP will be randomized to receive intravenous pentamidine as second-line therapy due to intolerance of or contraindications to trimethoprim-sulfamethoxazole.

Drug: Pentamidine

Mild to Moderate PCP- Clindamycin+primaquine

EXPERIMENTAL

Participants with mild to moderate PCP will be randomized to receive clindamycin in combination with primaquine as second-line therapy due to intolerance of or contraindications to trimethoprim-sulfamethoxazole.

Drug: Clindamycin + primaquine

Mild to moderate PCP- Atovaquone

EXPERIMENTAL

Participants with mild to moderate PCP will be randomized to receive atovaquone as second-line therapy due to intolerance of or contraindications to trimethoprim-sulfamethoxazole.

Drug: Atovaquone

Interventions

Clindamycin + primaquine DRUG

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.

Mild to Moderate PCP- Clindamycin+primaquine; Severe PCP-Clindamycin+primaquine

Pentamidine DRUG

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)

Severe PCP-Intravenous Pentamidine

Atovaquone DRUG

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).

Mild to moderate PCP- Atovaquone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Immunocompromised patients (including but not limited to HIV, solid organ transplant, solid tumors, hematological transplant and malignancies, systemic diseases, chemotherapy, long term corticosteroid use, and immunosuppressive therapies, as well as primary immunodeficiencies) in an emergency department, cliinic, or hospital
• Age ≥18 years
• Proven or probable Pneumocystis jirovecii pneumonia
• Inability to receive trimethoprim-sulfamethoxazole due to contraindication, intolerance, toxicity, or treatment failure
• Immunocompromised status
• Ability to provide informed consent (or per local regulations)
• While participants may be enrolled in multiple domains of the SPIRIT-PCP Platform over time (if they are eligible and a domain is active), they may only be enrolled to single question once (e.g., they can be part PCP Alternatives and an eventual secondary prophylaxis domain; however, if they have a recurrence, they cannot be included in PCP Alternatives again).

You may not qualify if:

• The Platform will exclude: patients where we are unable to obtain informed consent, where patients or their proxy have declined to consent, where the treating team has declined participation, where follow up cannot be reliably obtained (e.g., lack of means of communication, patient non-resident of jurisdiction), where treatment with antibiotics is not in keeping with a patient's advanced care directives, and where death is deemed imminent (\<48h) as determined by the treating team and site investigator.
• Clinical:
• Previous severe adverse reaction or hypersensitivity to clindamycin, primaquine, or atovaquone (mild-moderate PCP) or to clindamycin, primaquine, or pentamidine (severe PCP);
• More than 7 calendar days of any therapy for PCP (no more than 4 can involve a study drug).
• Known pregnancy or breastfeeding (pregnancy test will be offered)
• For clindamycin-primaquine:
• Known G6PD deficiency OR family history of G6PD deficiency without excluding by testing\*
• Known diagnosis of porphyria
• Concomitant use of methotrexate or cyclophosphamide which cannot be held \*G6PD deficiency is an X-linked recessive genetic disease. Female patients without a family history are very unlikely to have this disease and so therapy can start while waiting for the test in the absence of a family history. Male patients should wait for test results prior to receiving primaquine even if they do not have a family history. For those without G6PD testing at diagnosis, it is a reasonable standard of care to order testing.
• For pentamidine:
• Absence of adequate intravenous access as determined by treating team and site investigator. In the event of loss of IV, up to 2 consecutive doses can be given intramuscularly if the patient is not systemically anticoagulated and does not have a coagulopathy.
• Hypotension defined as systolic blood pressure below 90mmHg without pharmacologic support
• Personal history of Torsade de Pointes or presence of a corrected QTc of greater than 490ms on ECG on date of enrollment
• For atovaquone:
• Receipt of PCP Prophylaxis (≥3 doses per week) for ≥ 4 weeks with atovaquone

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead

Related Publications (3)

• Del Corpo O, Butler-Laporte G, Sheppard DC, Cheng MP, McDonald EG, Lee TC. Diagnostic accuracy of serum (1-3)-beta-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect. 2020 Sep;26(9):1137-1143. doi: 10.1016/j.cmi.2020.05.024. Epub 2020 May 30.

  PMID: 32479781 RESULT

• McDonald EG, Afshar A, Assiri B, Boyles T, Hsu JM, Khuong N, Prosty C, So M, Sohani ZN, Butler-Laporte G, Lee TC. Pneumocystis jirovecii pneumonia in people living with HIV: a review. Clin Microbiol Rev. 2024 Mar 14;37(1):e0010122. doi: 10.1128/cmr.00101-22. Epub 2024 Jan 18.

  PMID: 38235979 RESULT

• McDonald EG, Butler-Laporte G, Del Corpo O, Hsu JM, Lawandi A, Senecal J, Sohani ZN, Cheng MP, Lee TC. On the Treatment of Pneumocystis jirovecii Pneumonia: Current Practice Based on Outdated Evidence. Open Forum Infect Dis. 2021 Oct 29;8(12):ofab545. doi: 10.1093/ofid/ofab545. eCollection 2021 Dec.

  PMID: 34988242 RESULT

MeSH Terms

Conditions

Pneumonia, Pneumocystis; Pneumocystis Infections; Infections; Pneumonia

Interventions

Clindamycin; Primaquine; Pentamidine; Atovaquone

Condition Hierarchy (Ancestors)

Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Lincomycin; Lincosamides; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glycosides; Carbohydrates; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzamidines; Amidines; Organic Chemicals; Naphthoquinones; Quinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Emily G McDonald, MD MSc

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Todd C Lee, MD MPH

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

• Matthew P Cheng, MD FRCPC

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Babykumari Chitramuthu, PhD

CONTACT

15149341934; babykumari.chitramuthu@muhc.mcgill.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor of Medicine

Study Record Dates

• First Submitted: December 27, 2025
• First Posted: January 21, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2029
• Study Completion (Estimated): September 1, 2029
• Last Updated: January 21, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Access Criteria: Contact emily.mcdonald@mcgill.ca; scientists seeking to answer secondary questions about the data or combine the data in a systematic review or meta-analysis. They can access anonymous individual patient data. There will need to be an inter-institutional data sharing agreement in place.