Effect of Steroids During Pneumocystis Infection Among Non HIV Immunocompromised Patients

Study Overview
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Brief Summary
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Pneumocystis jiroveci pneumonia (PcP) increased in non HIV immunocompromised patients. Mortality remains high for those patients with comorbidities (50% for patients with the most severe Pneumocystis pneumonia). Physiopathology, characteristics and outcome of PcP in non-HIV patients remains different from those in HIV patients. Steroids in HIV patients with PcP has been associated with decreased mortality but in non-HIV patients, adjunctive steroids remains controversy. Some retrospective studies in that field did not find any beneficial effects of steroids ((1mg/kg/jour d'Equivalent Prednisone (EP)). However, all the studies were retrospective, non randomised studies including various underlying disease and severity of PcP was variable. Moreover, dosage and delay of steroids were variable leading difficult to interpret all the results. The investigators want to demonstrate the beneficial effect of steroid during PcP in non-HiV immunocompromised patients with a double blinded randomised clinical trials comparing adjunctive steroids to placebo.

Official Title
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Intérêt de la corticothérapie Dans la Pneumocystose Grave du Patient immunodéprimé Non VIH. Essai Prospectif Multicentrique Randomisé Contrôlé : PIC

Conditions
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Pneumocystis, Steroids, Immunocompromised Patient, Hematologic Neoplasms, Immunosuppressive Agents, Neoplasms

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Severe PcP : 1 / interstitial acute pneumonia with possible or typical criteria for PcP and positive specimen for Pneumocystis jirovecii (excluding PCR) ; or interstitial acute pneumonia with typical criteria for PcP and positive PCR in respiratory specimen. 2/ Arterial pression of Oxygen (PaO2) < 60 mmHg on room air need of 3 L/min oxygen for saturation >92% or tachypnea>30min need of mechanical ventilation for acute respiratory failure. Treatment for PcP started for less than 7 days. Non-HIV immunosuppression : malignant hematological disease, solid tumor cured for less than 5 years, allogenic stem cell transplant, Steroids (>0.3mg/kg equivalent prednisone for more than 3 weeks or > 20mg/days for more than one months) or other immunosuppressive treatment for more than one months or solid organ transplantation. Signed inform consent by patient or relatives Health insurance Exclusion Criteria: HIV Serology HIV 1 or 2 positive Need of steroid ≥1mg/kg/j equivalent prednisone for another pathology (acute Graft versus Host disease (GVH= for example) Contra-indication for steroids Pregnancy of breath-feeding Denied to participate No health insurance tutelage

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Saline serum, same volume as in the Experimental arm. | Drug: Placebo<br>* saline serum<br>|
| Experimental: Steroids<br>Methylprednisolone intra veinous Day 1 to 5 : 30mg twice per day Day 6 to 10 : 30mg per day Day 11 to 21 : 20mg per day | Drug: Methylprednisolone<br>* Methylprednisolone intra veinous Day 1 to 5 : 30mg twice per day Day 6 to 10 : 30mg per day Day 11 to 21 : 20mg per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 28 days mortality after the randomisation | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 90 days mortality after the randomisation | Day 90 | 
| Hospital mortality | Mortality at hospital discharge | Day 120 | 
| ICU mortality | For patients admitted to ICU at ICU discharge | Day 90 | 
| Acute respiratory failure | Acute respiratory failure during treatment defined by one of those criteria within 28 days : Increased need of oxygen (more than 9 l/min of high flow nasal oxygen with Inspired Fraction of Oxygen (fiO2) >50%) Admission to ICU after randomisation Need of mechanical ventilation (invasive or non invasive) or high flow nasal oxygen | Day 28 | 
| Duration of mechanical ventilation | Duration of mechanical ventilation invasive and/or non invasive | Day 28 | 
| Occurrence of septic shock | septic shock is defined as need for vasopressor | Day 28 | 
| acute kidney injury | KDIGO score >=1 | Day 28 | 
| Hospital acquired infectious disease | Global incidence incidence of infections. Incidence of pulmonary or extra-pulmonary infections. Incidence of bacterial, viral and fungal infections. Diagnosis of infectious disease will be defined by the need of treatment. | Day 28 | 
| Hospital length of stay | Hospital length of stay at hospital discharge | Day 120 | 
| ICU length of stay | ICU length of stay at ICU discharge | Day 90 | 
| Duration of Insulin treatment | Insulin treatment is defined : patient without insulin treatment before study : start of insulin therapy patient treated with insulin before study : increased dose (>30%) of insulin | Day 28 |