Effectiveness of Intravenous Immunoglobulins (IVIG) in Toxic Shock Syndromes in Children (IGHN2)

Civil Hospices of Lyon

Status and phase: Withdrawn; Phase 4

Conditions: Staphylococcal Infection; Streptococcal Infection

Treatments: Drug: Albumin; Drug: PRIVIGEN (CSL Behring)

Study type: Interventional

Funder types: Other

Identifiers

NCT02899702

69HCL16_0079

Details and patient eligibility

About

IGHN2 is an international, multicenter, double blind, randomized controlled trial aimed at assessing the efficacy on organ dysfunctions of Intravenous Immunoglobulins (IVIG) treatment in the acute phase of streptococcal or staphylococcal toxic shock syndrome in children.

Sex: All

Ages: 1 month to 17 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 2 patient groups, including a placebo group

IVIG

Experimental group

Description:

PRIVIGEN (CSL Behring) NORMAL HUMAN IMMUNOGLOBULINS L-PROLINE, Water for injection

Treatment:

Drug: PRIVIGEN (CSL Behring)

control

Placebo Comparator group

Description:

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.

Treatment:

Drug: Albumin