Clinical Trial Corticoids For Empyema And Pleural Effusion In Children

Study Overview
=================
Brief Summary
-----------------
STUDY JUSTIFICATION Scientific evidence of the usefulness of corticosteroid use for infectious diseases: Corticosteroids along with antibiotic use improve survival in some infectious processes provide long term benefits and improve symptoms in many others. Clinical Observation: the investigators observed that patients with parapneumonic pleural effusion and associated bronchospasm who were treated with corticosteroids for their bronchospasm, evolved to healing before patients who were not treated with corticosteroids (average admission days 10 vs. 17). Rationale: the anti-inflammatory effect has been the rationale for the use of dexamethasone as an inhibitor of the inflammatory response observed after the first dose of parenteral antibiotic in bacterial meningitis. A similar effect is likely to occur in pneumonia with pleural effusion. It can be therefore hypothesized that Dexamethasone could inhibit an excessive inflammatory response by mesothelial and inflammatory cells during the early phases of parapneumonic empyema, reducing its severity and hence its complications. OBJECTIVES Principal: to investigate if dexamethasone 0,25mg/kg q.i.d. added to standard antibiotic therapy reduces time to resolution of parapneumonic pleural effusion. Secondary: 2.1. Evaluate the effect of dexamethasone 0,25mg/kg q.i.d. added to standard antibiotic therapy on the development of complications during pleural effusion episode. 2.2. Evaluate the incidence of severe and non severe adverse events associated with the new treatment versus standard therapy. METHODS Study design: exploratory (pilot), randomized, double blinded, placebo controlled, parallel stratified design, multicentric. Participating Hospitals (n=56, 7 patients per center): Hospital Infanta Sofía (S. Sebastián de los Reyes, Madrid). Hospital Universitario de Getafe Hospital Universitario Ramón y Cajal, Madrid. Hospital Universitario Materno-Infantil Carlos Haya, Málaga. Hospital Infantil La Paz, Madrid. Hospital U. Gregorio Marañón Hospital U. Príncipe de Asturias Hospital Virgen de la Salud, Toledo Endpoints: 3.1. Primary: time to resolution. 3.2. Secondary endpoints: Effectiveness: number of children with complications. Safety (expected number: none). i) Hyperglycemia ii) Signs of gastrointestinal bleeding iii) Need of transfusion iv) Oropharyngeal Candidiasis v) Allergic reaction vi) Other adverse reactions described in the Medication Guide. Treatment arms: 3.1. Control (0) Normal saline 0,6 ml/kg, IV, q.i.d. for 2 days. Cefotaxime 150 mg/kg, IV, q.d. until discharge criteria are present. Ranitidine 5 mg/kg IV, q.d. for 2 days. Amoxicillin- Clavulanic acid 80mg/kg p.o., q.d. during 15 days. 3.2. Study treatment: (1) dexamethasone 0,25mg/kg, IV, q.i.d. for 2 days. Cefotaxime 150 mg/kg, IV, q.d. until discharge criteria are present Ranitidine 5 mg/kg IV, q.d. for 2 days Amoxicillin/Clavulanic acid orally (80mg/kg/day) during 15 days. 4. INCLUSION CRITERIA Patients between 1 and 14 year old. Presence of pneumonia diagnosed by clinical and radiographic criteria: cough, fever and radiological consolidation. Evidence of pleural effusion.

Official Title
-----------------
MULTICENTRIC, PHASE II, CLINICAL TRIAL CORTICOIDS FOR EMPYEMA AND PLEURAL EFFUSION IN CHILDREN

Conditions
-----------------
Parapneumonic Pleural Effusion, Empyema

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients between 1 and 14 year old. Presence of pneumonia diagnosed by clinical and radiographic criteria: cough, fever and radiological consolidation. Evidence of pleural effusion. Exclusion Criteria: Allergy to any of the drugs included in the study. Immunodeficiency.

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 14 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: Dexamethasone<br>Dexamethasone 0,25mg/kg, IV, q.i.d. for 2 days. Cefotaxime 200 mg/kg, IV, q.d. until discharge criteria are present Ranitidine 5 mg/kg IV, q.d. for 2 days Amoxicillin/Clavulanic acid orally (80mg/kg/day) during 15 days. | Drug: Dexamethasone<br>* Dexamethasone 0,25mg/kg, IV, q.i.d. for 2 days. Cefotaxime 200 mg/kg, IV, q.d. until discharge criteria are present Ranitidine 5 mg/kg IV, q.d. for 2 days Amoxicillin/Clavulanic acid orally (80mg/kg/day) during 15 days.<br>|
| Placebo Comparator: Placebo<br>Normal saline 0,6 ml/kg, IV, q.i.d. for 2 days. Cefotaxime 200 mg/kg, IV, q.d. until discharge criteria are present. Ranitidine 5 mg/kg IV, q.d. for 2 days. Amoxicillin- Clavulanic acid 80mg/kg p.o., q.d. during 15 days. | Drug: Placebo<br>* Normal saline 0,6 ml/kg, IV, q.i.d. for 2 days. Cefotaxime 200 mg/kg, IV, q.d. until discharge criteria are present. Ranitidine 5 mg/kg IV, q.d. for 2 days. Amoxicillin- Clavulanic acid 80mg/kg p.o., q.d. during 15 days.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to resolution | days from diagnosis until criteria for cure | 1 month after admission | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of children with complications. | number of children with complications. | 3 months after diagnosis | 
| Number of children with complications attributable to corticoids | Hyperglycemia Signs of gastrointestinal bleeding Need of transfusion Oropharyngeal Candidiasis Allergic reaction | 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pleural effusion, empyema, corticoids, dexamethasone