Glucocorticoid Therapy Impact on the Inflammatory Response and Clinical Evolution in Patients With Severe Bronchiolitis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to to demonstrate that a 7-day course of systemic glucocorticoids decreases the inflammatory activity of moderate or severe bronchiolitis in paediatric patients compared to the standard treatment. To evaluate the morbidity (regarding to the clinical course: Intensive Pediatric Unit Care unit (PICU) admission, mechanical ventilation, ionotropic support, nosocomial infection, rescue therapy for respiratory failure; duration of PICU stay and hospitalization; and exitus) between the treatment and the control groups.

Detailed Description
-----------------
A Prospective, randomised, double blind and placebo controlled study. Patients assigned to experimental group (group 1) will receive iv methylprednisolone 2 mg/kg/day (in two divided doses) and/or oral prednisolone 2,5 mg/kg/day (in two divided doses) every 12 hours, during 7 days. Patients assigned to control group (group 2) will receive iv/oral glucose 5% solution as placebo, at the same dose and time as the experimental group. A total of 50 (initially 39, but it was extended to 50 by Protocol Amendment) patients per group are recruited. Bronchiolitis is the most common infection of the lower respiratory tract. It is defined as, the first episode of bronchospasm, dyspnea, expiratory difficulty, feed refusal, tachypnea greater than 50 rpm and radiological evidence of hyperinflation, in less than 24 months. It is a very prevalent disease, Respiratory syncytial virus (RSV) infects 70% of children under one year and 100% of children under 2 years and generates a major health impact on epidemic period (especially from December to February) . It is the most frequent cause of hospitalization in children under one year during the winter and up to 10% of those admitted will need intensive care, of which up to 60% required intubation and mechanical ventilation. The estimated disease in healthy children, mortality ranges from 0.005% to 0.02%, while in hospitalized children becomes between 1% and 3%. In recent years, there have been numerous studies, mainly in RSV bronchiolitis, to analyze the immunological basis of the disease, as discussed complex, in order to perform a prophylaxis and treatment of more optimal infection. Inflammatory response in bronchiolitis results in activation of cytokines and chemokines that generates a viral clearance. However, if the inflammatory response is disproportionate, the pathogenesis of the disease can lead to a worse clinical evolution. Corticosteroids are drugs having inhibitory effects on specific immune response, mediated both T cells and the B cell, and are potent inhibitors of phagocyte function. These drugs are effective in the management of multiple forms of secondary inflammatory diseases or immune disorders and may also be useful in the management of bronchiolitis. The treatment of bronchiolitis is mainly based on supportive therapy: oxygen therapy, proper hydration and aspiration of nasal secretions. Many treatments have been tried that have tried to lessen the severity of the infection, such as the use of bronchodilators and / or corticosteroids, although with controversial results. In the literature review conducted in PubMed, the investigators found about 110 related bronchiolitis, as MeSH Terms, publications using the words bronchiolitis [All Fields] AND (child [MeSH Terms]. Only three of these articles shows results of clinical trials, although none in relation to the usefulness of steroids in bronchiolitis. There is just a case report describing the use of intravenous corticosteroids in infants with severe bronchiolitis, in combination with therapies such as extracorporeal oxygenation. One of the important aspects that the investigators took in consideration is that rhinovirus bronchiolitis is one of the most involved cause in the development of asthma, and just one of the etiologies of bronchiolitis who could benefit from treatment with corticosteroids. Prednisolone and methylprednisolone are also well known and used drugs, whose side effects are often dose and duration dependent. The identification and recruitment of patients will take place during the admission in the Intensive Pediatric Unit Care unit at the Hospital Sant Joan de Deu. Treatment of patients starts on days 0 and 3 of hospitalization. The patient treatment duration is 7 days, after that starts the follow-up phase, which duration is one month from the date of the baseline visit and until the hospital discharge.

Official Title
-----------------
Impact of the Administration of Systemic Glucocorticoids on Inflammatory Response and Clinical Evolution of Patients Diagnosed With Moderate- Severe Bronchiolitis

Conditions
-----------------
Bronchiolitis, Viral

Intervention / Treatment
-----------------
* Drug: Glucocorticoids
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The study will recruit paediatric patients younger than one year old who require hospitalization for moderate-severe bronchiolitis according to the BRONCHIOLITIS SCORE of Sant Joan de Deu Hospital (HSJD) Exclusion Criteria: Patients of either gender under one year old with mild bronchiolitis. Patients with bronchiolitis in which the principal symptom is apnoea. Patients who have received corticotherapy before admission to hospital. No consent from parents or tutors. Patients with previous acquired or innate immunodepression. Patients enrolled in other clinical trials.

Ages Eligible for Study
-----------------
Maximum Age: 12 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: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glucocorticoids<br>methylprednisolone intravenous administration of 2mg/kg/day (divided in two doses) and/or oral prednisolone 2,5 mg/kg/day (in two divided doses) during 7 days. Patients younger than 2 year, who required hospitalization, affected by moderate or severe bronchiolitis | Drug: Glucocorticoids<br>* Patients assigned to experimental group (group 1) will receive iv methylprednisolone 2 mg/kg/day (divided in two doses) doses and/or oral prednisolone 2,5 mg/kg/day (divided in two doses) during 7 days.<br>* Other names: ESTILSONA Gotas;|
| Placebo Comparator: Placebo<br>will receive iv/oral glucose 5% solution as placebo of 2mg/kg/day and/or 2,5 mg/kg/day (divided in two doses) during 7 days. Patients younger than 2 year, who required hospitalization, affected by moderate or severe bronchiolitis. | Other: Placebo<br>* Patients assigned to control group (group 2) will receive iv/oral glucose 5% solution as placebo, 2 mg/kg/day (divided in two doses) during 7 days.<br>* Other names: Plast-Apyr Glucosado 5%;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in inflammatory response | inflammatory response evaluation of the first week of glucocorticoids treatment as assessed by multiple measurements aggregated to arrive at one reported value, which are: the bronchiolitis clinical severity Scale, pediatric mortality Risk scale (PRISM III), the Chest x-ray test, the nasopharyngeal aspiration and analytical exploration (at day 5-7) | enrollment to one week treatment | 
| Morbidity episodes | Morbidity assessment by multiple measurements aggregated to arrive at one reported value which are as follow: necessity of mechanical ventilation, inotropic, presence of nosocomial infection, rescue therapies if respiratory failure occur; days of admission to the Pediatric Intensive Care Unit and hospitalization, in both treatment and control groups | 14 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Side effects estimate | Number of Side effects estimate by comparing the experimental group to the control group | 14 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Respiratory viral infection., Respiratory syncytial virus bronchiolitis, METHYLPREDNISOLONE SODIUM SUCCINATE