Effectiveness of Intravenous Immunoglobulins (IVIG) in Toxic Shock Syndromes in Children

Recruitment & Eligibility

Inclusion Criteria

Child/adolescent: 1 month < Age < 17 year-old,
admitted to PICU with a strong suspicion of staphylococcal or streptococcal infection; at least one following criterion, with at least one following criteria:
1. Toxic Shock Syndrom as defined by Centre for Disease Control criteria
2. or group A Streptococcus necrotizing fasciitis (positive streptest)
3. or varicella with infected lesions and rash or positive streptest
4. or erythrodermic rash in menstrual period
5. or pleuropneumonia with erythrodermic rash or positive streptest in pleural fluid
6. or erythrodermic rash and biological fluid positive to streptococcus A or staphylococcus (articular, pericardial, bronchopulmonary, pharynx)
With shock resistant to fluid resuscitation, defined as existence, despite 40 ml/kg of fluid bolus within 1 hour, of:
1. hypotension (< 5th percentile)
2. or systolic blood pressure < 2 SD regarding age
3. or need for vasoactive drugs in order to maintain blood pressure at a normal level (dopamine > 5µg/kg/min or dobutamine, adrenaline, noradrenaline, milrinone whatever the dose)
4. or 2 signs of hypo perfusion among:
  1. metabolic acidosis with base deficit > 5
  2. lactate x 2 normal laboratory value
  3. diuresis < 0,5 ml/kg/h
  4. capillary refill time > 5 sec
  5. Skin/central temperature difference > 3°C
With informed consent signed by at least one parent before any procedures or treatments related to the study.

Exclusion Criteria

First signs of shock appeared more than 24h ago
Known hypersensitivity to one of the components (study treatment or placebo , see below)
Hypersensitivity to homologous immunoglobulins, specifically in very rare cases of Ig A deficit, when the patient has anti-IgA antibodies
Known hyperprolinemia
Immunodeficiency (acquired or not),
Immunosuppressive drugs
No health cover

Study & Design

Arm && Interventions

Group	Intervention	Description
IVIG	PRIVIGEN (CSL Behring)	PRIVIGEN (CSL Behring) NORMAL HUMAN IMMUNOGLOBULINS L-PROLINE, Water for injection
control	Albumin	Single administration of Albumin 4% diluted albumin (LFB), within 12 hours following PICU admission (or outbreak of first shock signs). Isovolume - so dose of 0.8 g/kg We chose as placebo albumin diluted to 4% because this solution has the advantage of having a comparable osmolality. The treatment of toxic shock will be standardized. It consists of antibiotics: Amoxicillin-clavulanate and clindamycin (or Rifampicin, Rifadine® if allergic). Antibiotics are not considered as experimental treatments for this study. All treatments essential for the treatment of acute condition will be allowed and are not considered as experimental treatments for this study.

Primary Outcome Measures

Name	Time	Method
organ dysfunctions	between day of admission and day 3	Average variation in Pediatric Logistic Organ Dysfunction 2 ( PELOD-2) score compared between the IVIG treatment arm and the placebo arm.

Secondary Outcome Measures

Name	Time	Method
organ dysfunctions assessed by the PELOD-2 score	over the first 5 days in Paediatric Intensive Care Unit (PICU)
disability assessed by the Pediatric Overall Performance Category (POPC) score	one year after recruitment
impairment assessed by the Vineland Adaptive Behavior Scale 2 (VABS II)	one year after recruitment
global mortality	1 year

Recruitment & Eligibility