Clinical Trial Corticoids For Empyema And Pleural Effusion In Children (CORTEEC)

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

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.

Study Overview

• Status: Completed
• Conditions: Empyema; Parapneumonic Pleural Effusion
• Intervention / Treatment: Drug: Dexamethasone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Spain
  • Madrid, Spain
    • Hospital Ramón y Cajal
  • Madrid, Spain
    • Hospital Universitario Gregorio Maranon
  • Madrid, Spain, 28037
    • Hospital Infantil La Paz
  • Andalucia
    • Malaga, Andalucia, Spain
      • Hospital Carlos Haya
  • Castilla La Mancha
    • Toledo, Castilla La Mancha, Spain
      • Complejo Hospitalario Toledo
  • Madrid
    • Alcalá de Henares, Madrid, Spain
      • Hospital Principe de Asturias
    • Getafe, Madrid, Spain
      • Hospital Universitario de Getafe
    • San Sebastián de los Reyes, Madrid, Spain, 28014
      • Hospital Infanta Sofia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 14 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dexamethasone; 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; 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.
Placebo Comparator: Placebo; 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; 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.

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

Collaborators and Investigators

• Sponsor: Hospital Infanta Sofia
• Collaborators: Pediatrics Spanish Association (Madrid and Castilla-La Mancha Pediatric Association); Spanish Ministry of Health.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: December 15, 2010
• First Submitted That Met QC Criteria: December 15, 2010
• First Posted (Estimate): December 16, 2010

Study Record Updates

• Last Update Posted (Estimate): June 1, 2015
• Last Update Submitted That Met QC Criteria: May 29, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: pleural effusion, empyema, corticoids, dexamethasone
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Diseases; Inflammation; Pleural Diseases; Suppuration; Pleural Effusion; Empyema; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: Hospital Infanta Sofia; 2009-012963-33 (EudraCT Number)