Please select the eligibility criteria that correspond to the clinical trial below.
Title: MULTICENTRIC, PHASE II, CLINICAL TRIAL CORTICOIDS FOR EMPYEMA AND PLEURAL EFFUSION IN CHILDREN
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.


Options:
A: 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.
B: Inclusion Criteria:

* Age 18 years and older
* Diagnosis of severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference 1992
* Diagnosis of acute lung injury or acute respiratory distress syndrome according to the American-European Consensus Conference on ARDS 1994
* Onset of organ dysfunction within 12 hours before enrollment

Exclusion Criteria:

* Indicated for receive corticosteroid
* Congestive heart failure
* Contra-indication for hydrocortisone: For example: allergy to hydrocortisone
* Pregnancy
* Not agree to sign the consent form
C: Inclusion Criteria:

1. Clinical evidence of infection within the previous 72 hours (may be present longer than 72 hours) (a, b, c, or d - only 1 required)

   1. Presence of polymorphonuclear cells in a normally sterile body fluid (excluding blood);
   2. Culture or Gram stain of blood, sputum, urine or normally sterile body fluid positive for a pathogenic micro-organism;
   3. Focus of infection identified by visual inspection (e.g. ruptured bowel with the presence of free air or bowel contents in the abdomen found at the time of surgery, wound with purulent drainage);
   4. Other clinical evidence of infection - treated community acquired pneumonia, purpura fulminans, necrotising fascitis, etc.
2. Evidence of a systemic response to infection as defined by the presence of two or more of the following signs within the previous 24 hours. These signs may be present longer than 72 hours.

   1. Fever (temperature \>38.3°C) or hypothermia (rectal temperature \< 35.6°C);
   2. Tachycardia (heart rate of \>90 beat/min);
   3. Tachypnea (respiratory rate \> 20 breaths/min, PaC02\<32 mmHg) or patient requires invasive mechanical ventilation;
   4. Alteration of the WBC count \>12,000 cells/mm3, \<4,000 cells/mm3 or \>10% immature neutrophils (bands).
3. Evidence of shock defined by (A + B- both required within the previous 72 hours (may NOT be present longer than 72 hours).

A. A systolic blood pressure \< 90 mmHg or a decrease in SBP of more than 50 mmHg from baseline in previous hypertensive patients (for at least one hour) despite adequate fluid replacement OR need for vasopressors for at least one hour (infusion of dopamine ≥ 5 mcg/kg/min or any dose of adrenaline, noradrenaline, phenylephrine or vasopressin) to maintain a SBP ≥ 90 mmHg;

B. Hypoperfusion or organ dysfunction which is not the result of underlying diseases or drugs, but is attributable to sepsis, including one of the following:

1. Sustained oliguria (urine output \< 0.5 ml/kg/hr for a minimum of 1 hour)
2. Metabolic acidosis \[pH of \< 7.3, or a base deficit of \> or = 5.0 mmol/L, or an increased lactic acid concentration (\> 2 mmol/L)\].
3. Arterial hypoxemia (Pa02/FI02\<280 in the absence of pneumonia)(Pa02/FI02\<200 in the presence of pneumonia).
4. Thrombocytopenia - platelet count ≤ 100,000 cells/mm3.
5. Acute altered mental status (Glasgow Coma Scale \< 14 or acute change from baseline).

4. Informed Consent

5. Cortisol level at baseline and 60 minutes after 0.25 mg cosyntropin

Exclusion Criteria:

1. Pregnancy
2. Age less than 18.
3. Underlying disease with a prognosis for survival of less than 3 months.
4. Cardiopulmonary resuscitation within 72 hours before study.
5. Drug-induced immunosuppression, including chemotherapy or radiation therapy within 4 weeks before the study.
6. Administration of chronic corticosteroids in the last 6 months or acute steroid therapy (any dose) within 4 weeks (including inhaled steroids). Topical steroids are not exclusions.
7. HIV positivity.
8. Presence of an advanced directive to withhold or withdraw life sustaining treatment (i.e. DNR).
9. Advanced cancer with a life expectancy less than 3 months.
10. Acute myocardial infarction or pulmonary embolus.
11. Another experimental drug study within the last 30 days.
12. Moribund patients likely to die within 24 hours.
13. Patients in the ICU for more than 2 months at the time of the start of septic shock.
D: Inclusion Criteria:

* Diagnosed with ARDS or has risk factors for ARDS; individuals will be considered at risk if they are critically ill and have trauma, sepsis, shock, pneumonia, inhalation injury, drug overdose, pancreatitis, or hypertransfusion
* Onset of ARDS must be between 7 and 28 days prior to study entry
* Since ARDS onset, bilateral infiltrates must have persisted and participants must have required continuous mechanical ventilation

Answer: A