Effect of Steroids During Pneumocystis Infection Among Non HIV Immunocompromised Patients

Phase 3

• Conditions: Hematologic Neoplasms; Immunosuppressive Agents; Steroids; Neoplasms; Immunocompromised Patient; Pneumocystis
• Interventions: Drug: Placebo; Drug: Methylprednisolone

• Registration Number: NCT02944045
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-10-17
• Study First Submitted QC: 2016-10-24
• Study First Posted: 2016-10-25
• Study Start: 2017-02-15
• Status Verified: 2020-10
• Last Update Submitted: 2020-10-05
• Last Update Posted: 2020-10-06
• Primary Completion: 2021-10
• Study Completion: 2022-10

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 222

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Saline serum, same volume as in the Experimental arm.
Steroids	Methylprednisolone	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

Primary Outcome Measures

Name	Time	Method
Mortality	Day 28	28 days mortality after the randomisation

Secondary Outcome Measures

Name	Time	Method
Occurrence of septic shock	Day 28	septic shock is defined as need for vasopressor
ICU length of stay	Day 90	ICU length of stay at ICU discharge
Hospital mortality	Day 120	Mortality at hospital discharge
Hospital length of stay	Day 120	Hospital length of stay at hospital discharge
ICU mortality	Day 90	For patients admitted to ICU at ICU discharge
acute kidney injury	Day 28	KDIGO score \>=1
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.
Mortality	Day 90	90 days mortality after the randomisation
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
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

Trial Locations

Locations (1)

Medical ICU; 🇫🇷 Paris, France