Health TrialsbyHealthPanel

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

ConditionsPneumocystisPneumocystis InfectionPneumocystis Carinii InfectionPneumocystis Carinii; Infection, Resulting From HIV DiseasePneumocystis Jirovecii PneumoniaPneumocystis Jirovecii InfectionPneumocystosis Associated With AIDSPneumocystosis; Pneumonia (Etiology)
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorMcGill University Health Centre/Research Institute of the McGill University Health Centre

About this trial

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?

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

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)

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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.

  • 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)

  • 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).

Treatment groups

416 Participants
are divided into 4 treatment groups
Group A: Severe PCP-Clindamycin+primaquineExperimental treatment 1 intervention
Group B: Severe PCP-Intravenous PentamidineExperimental treatment 1 intervention
Group C: Mild to Moderate PCP- Clindamycin+primaquineExperimental treatment 1 intervention
Group D: Mild to moderate PCP- AtovaquoneExperimental treatment 1 intervention

Trial outcomes

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)

Time frame
Day 30

Secondary outcomes

1

Proportion of patients that die (death)

Mortality at day 30

Time frame
Day 30
2

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

New initiation of extracorporeal membrane oxygenation during hospitalization following initiation of assigned PCP treatment strategy.

Time frame
Day 30
3

Proportion of patients requiring new Invasive Mechanical Ventilation

Initiation of invasive mechanical ventilation via endotracheal intubation during hospitalization following initiation of the assigned PCP treatment strategy.

Time frame
Day 30
4

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

Proportion of patients with occurence of severe (CTCAE grade 4) adverse drug event (dermatologic, nephrologic, hematologic, neurologic, and/or endocrinologic) considered at least probable (by Leape and Bates criteria).

Time frame
Day 30

Other outcomes

1

Tertiary outcome measure of quality of life at day 30

Quality of life (EQ-5D-5L) wherein a higher score indicates better quality of life.

Time frame
Day 30
2

Tertiary outcome measure of all-cause mortality

All-cause mortality, defined as death from any cause.

Time frame
Day 180
3

Tertiary Outcome Measure of PCP recurrence

Recurrence of pneumocystis pneumonia, defined as a new episode of clinically and/or microbiologically confirmed PCP after initial resolution.

Time frame
Day 180
4

Tertiary Outcome measure of quality of life at day 180

Quality of life assessed using a EQ-5D-5L questionnaire. High score indicates better quality of life.

Time frame
Day 180

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

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

Lead sponsor

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: