Hematologic Neoplasms, Immunocompromised Patient, Immunosuppressive Agents, Neoplasms, Pneumocystis, Steroids
Conditions
Brief summary
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.
Interventions
DRUGMethylprednisolone
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
DRUGPlacebo
saline serum
Sponsors
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Day 28 | 28 days mortality after the randomisation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hospital mortality | Day 120 | Mortality at hospital discharge |
| ICU mortality | Day 90 | For patients admitted to ICU at ICU discharge |
| Acute respiratory failure | Day 28 | 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 |
| Duration of mechanical ventilation | Day 28 | Duration of mechanical ventilation invasive and/or non invasive |
| Occurrence of septic shock | Day 28 | septic shock is defined as need for vasopressor |
| Mortality | Day 90 | 90 days mortality after the randomisation |
| Hospital acquired infectious disease | Day 28 | 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. |
| Hospital length of stay | Day 120 | Hospital length of stay at hospital discharge |
| ICU length of stay | Day 90 | ICU length of stay at ICU discharge |
| Duration of Insulin treatment | Day 28 | 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 |
| acute kidney injury | Day 28 | KDIGO score \>=1 |
Countries
France
Contacts
Primary ContactVirginie Lemiale, MD
Backup ContactMatthieu Resche-Rigon, MD PHD
Outcome results
None listed