Clinical trial NCT01261546: Clinical Trial Corticoids For Empyema And Pleural Effusion In Children
Official title: MULTICENTRIC, PHASE II, CLINICAL TRIAL CORTICOIDS FOR EMPYEMA AND PLEURAL EFFUSION IN CHILDREN
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parapneumonic Pleural Effusion
Empyema
Keywords: pleural effusion, empyema, corticoids, dexamethasone
Lead sponsor: Hospital Infanta Sofia
Sponsor class: OTHER
Collaborators: name: Pediatrics Spanish Association (Madrid and Castilla-La Mancha Pediatric Association)
name: Spanish Ministry of Health.
First posted: 2010-12-16
Enrollment: 60
Sex: ALL
Minimum age (years): 1
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: STUDY JUSTIFICATION

1. 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.
2. 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).
3. 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

1. Principal: to investigate if dexamethasone 0,25mg/kg q.i.d. added to standard antibiotic therapy reduces time to resolution of parapneumonic pleural effusion.
2. 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

1. Study design: exploratory (pilot), randomized, double blinded, placebo controlled, parallel stratified design, multicentric.
2. 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
3. Endpoints:

   3.1. Primary: time to resolution. 3.2. Secondary endpoints:
   1. Effectiveness: number of children with complications.
   2. 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.
4. 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.


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.

Primary outcomes:
measure: time to resolution
timeFrame: 1 month after admission
Secondary outcomes:
measure: number of children with complications.
timeFrame: 3 months after diagnosis
measure: Number of children with complications attributable to corticoids
timeFrame: 3 months
Other outcomes:
Locations:
city: Malaga
country: Spain
facility: Hospital Carlos Haya
state: Andalucia
city: Toledo
country: Spain
facility: Complejo Hospitalario Toledo
state: Castilla La Mancha
city: Alcalá de Henares
country: Spain
facility: Hospital Principe de Asturias
state: Madrid
city: Getafe
country: Spain
facility: Hospital Universitario de Getafe
state: Madrid
city: San Sebastián de los Reyes
country: Spain
facility: Hospital Infanta Sofia
state: Madrid
city: Madrid
country: Spain
facility: Hospital Infantil La Paz
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Marañón
Study officials:
References:
citation: Tagarro A, Otheo E, Baquero-Artigao F, Navarro ML, Velasco R, Ruiz M, Penin M, Moreno D, Rojo P, Madero R; CORTEEC Study Group. Dexamethasone for Parapneumonic Pleural Effusion: A Randomized, Double-Blind, Clinical Trial. J Pediatr. 2017 Jun;185:117-123.e6. doi: 10.1016/j.jpeds.2017.02.043. Epub 2017 Mar 28.