Low Doses Corticosteroids as Adjuvant Therapy for the Treatment of Severe H1N1 Flu

Study Overview
=================
Brief Summary
-----------------
The H1N1 flu pandemic is one of the major infectious threat of the past half century. it is rapidly progressing worldwide and a substantial number of patients get severe H1N1 related pneumonia that requires mechanical ventilation and admission to the intensive care unit. The acute respiratory distress syndrome is associated with a substantial mortality and morbidity partly as a consequence of uncontrolled lung and systemic inflammation. many physicians are trying to counteract this pro-inflammatory storm by the use of corticosteroids albeit these drugs may cause super infection or metabolic disorders. Thus, there is a need for a randomized double blind, placebo controlled trial to define the benefit to risk ratio of corticosteroids in this patient.

Official Title
-----------------
Phase III Study of Hydrocortisone in Patients With Severe H1N1 Related Pneumonia

Conditions
-----------------
Pneumonia, Viral, Influenza in Humans

Intervention / Treatment
-----------------
* Drug: hydrocortisone
* Drug: isotonic saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: age above 15 years old admitted to intensive care unit proven or strong suspicion of H1N1 Influenza infection diffuse pneumonia (for less than 96 hours) need for non invasive or invasive mechanical ventilation Exclusion Criteria: pregnancy an age of 15 or less rapidly fatal underlying disease with a life expectancy of one month or less more than 3 organ dysfunction upon admission previous treatment with corticosteroids (ie prednisone 30 mg per day or more, or equivalent, for at least one month) formal indication for corticosteroids (eg Addison disease, status asthmaticus) already on corticosteroids for 2 days or more in the management of the current episode acute lung injury not related to viral pneumonia presence of H1N1 related acute myocarditis or encephalitis receiving antiviral treatment for more than 5 days

Ages Eligible for Study
-----------------
Minimum Age: 15 Years

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Corticosteroids<br>Hydrocortisone | Drug: hydrocortisone<br>* 50mg intravenous bolus every 6 hours for one week, then every 12 hours for one week and then every 24 hours for one week<br>* Other names: hydrocortisone acetate;|
| Placebo Comparator: Control<br>isotonic saline | Drug: isotonic saline<br>* intravenous bolus every 6 hours for one week, then every 12 hours for one week and then every 24 hours for one week<br>* Other names: normal saline;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| in hospital all cause morality |  | hospital discharge up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 28 day mortality |  | 28 day | 
| 90 day all cause mortality |  | 90 day | 
| 6 month all cause mortality |  | 180 days | 
| mechanical ventilation free days |  | hospital discharge up to 90 days | 
| intensive care unit free days |  | hospital discharge up to 90 days | 
| proportion of patients with secondary infections |  | hospital discharge up to 90 days | 
| proportion of patients who require ECMO |  | hospital discharge up to 90 days | 
| respiratory function and health status |  | 180 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Acute lung injury, Acute respiratory distress syndrome, corticosteroids, inflammation