Pneumocystis Jerovici Pneumonia in Infants and Steroids

Study Overview
=================
Brief Summary
-----------------
This is a double-blind randomized controlled trial assessing the efficacy of adjuvant corticosteroids in clinically diagnosed Pneumocystis jiroveci pneumonia in infants.

Detailed Description
-----------------
The study aims to determine whether the early administration of adjuvant corticosteroids in addition to high dose oral Co-trimoxazole reduces mortality amongst infants aged 2-6 months with vertically acquired HIV and clinically diagnosed Pneumocystis jiroveci pneumonia. Infants will be randomized to receive either a steroid regime of oral prednisolone at 2 mg/kg for 7 days, then 1 mg/kg for 7 days, then 0.5mg/kg for 7 days for a total of 21 days or placebo.

Official Title
-----------------
Early Steroid Use in Infants With Clinical Pneumocystis Jiroveci Pneumonia (PCP) in the Queen Elizabeth Central Hospital, Blantyre, Malawi

Conditions
-----------------
Pneumonia, Pneumocystis Jerovici

Intervention / Treatment
-----------------
* Drug: Prednisone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Consecutive infants with HIV and clinical features of Pneumocystis jiroveci pneumonia who require oxygen (oxygen saturations in air < 90%). Clinical diagnosis of Pneumocystis jiroveci pneumonia will be made by one of the study investigators. All infants must be HIV ELISA positive or exposed, have an oxygen requirement (saturations on air < 90%) and have severe respiratory distress and cough. They may also have a low grade fever, clear chest or diffuse signs on auscultation and features suggestive of Pneumocystis jiroveci infection on chest radiography. Exclusion Criteria: Previous known allergy or hypersensitivity or other contraindication to corticosteroids or co-trimoxazole. Previous treatment for suspected Pneumocystis jiroveci pneumonia or a delay starting steroids for greater than 24 hours after starting high dose co-trimoxazole. Patients who are not exposed to HIV. Infants with known preexisting active pulmonary or cardiac disease. Patients who do not live within the Blantyre district and who are unable to attend follow up at QECH. Infants whose parents or guardians refuse consent.

Ages Eligible for Study
-----------------
Minimum Age: 2 Months
Maximum Age: 6 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prednisone versus placebo<br>Prednisone 2mg/kg orally once a day x 7 days, 1 mg/kg orally once a day x 7 days and then 0.5 mg/kg orally once a day x 7 days | Drug: Prednisone<br>* The steroid regime will be oral prednisone at 2 mg/kg for 7 days, then 1 mg/kg for 7 days, then 0.5mg/kg for 7 days for a total of 21 days.<br>Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction in inpatient mortality by 20%. | To determine whether the addition of oral Prednisolone to standard treatment reduces inpatient mortality by 20% in patients aged 2-6 months with clinical PJP pneumonia. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Commencement of antiretroviral treatment | To determine whether steroids significantly increase the number of patients that successfully commence anti-retroviral treatment. | 36 months | 
| 6 month survival | To determine whether steroids significantly increase the number of patients that survive to 6 months following commencement of anti-retrovirals. | 36 months | 
| Morbidity (days in hospital and days on oxygen) | To determine whether steroids significantly alter morbidity as determined by number of days spent in hospital as an inpatient and number of days on oxygen. | 36 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Pneumocystis Jiroveci, Steroids, Infants