Effect of Steroids During Pneumocystis Infection Among Non HIV Immunocompromised Patients (PIC)

October 5, 2020 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

222

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Saline serum, same volume as in the Experimental arm.
Drug: Placebo
saline serum
EXPERIMENTAL: Steroids

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

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: Day 90
90 days mortality after the randomisation
Day 90
Hospital mortality
Time Frame: Day 120
Mortality at hospital discharge
Day 120
ICU mortality
Time Frame: Day 90
For patients admitted to ICU at ICU discharge
Day 90
Acute respiratory failure
Time Frame: 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
Day 28
Duration of mechanical ventilation
Time Frame: Day 28
Duration of mechanical ventilation invasive and/or non invasive
Day 28
Occurrence of septic shock
Time Frame: Day 28
septic shock is defined as need for vasopressor
Day 28
acute kidney injury
Time Frame: Day 28
KDIGO score >=1
Day 28
Hospital acquired infectious disease
Time Frame: 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.
Day 28
Hospital length of stay
Time Frame: Day 120
Hospital length of stay at hospital discharge
Day 120
ICU length of stay
Time Frame: Day 90
ICU length of stay at ICU discharge
Day 90
Duration of Insulin treatment
Time Frame: 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
Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Study Director: Elie Azoulay, MD PHD, APHP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

February 15, 2017

Primary Completion (ANTICIPATED)

October 1, 2021

Study Completion (ANTICIPATED)

October 1, 2022

Study Registration Dates

First Submitted

October 17, 2016

First Submitted That Met QC Criteria

October 24, 2016

First Posted (ESTIMATE)

October 25, 2016

Study Record Updates

Last Update Posted (ACTUAL)

October 6, 2020

Last Update Submitted That Met QC Criteria

October 5, 2020

Last Verified

October 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P150961
  • 2016-002275-10 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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