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

NCT02899702 | Withdrawn Phase 4 DMC

• 1 other identifier: 69HCL16_0079
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Staphylococcal Infection; Streptococcal Infection

Outcome Measures

Primary Outcomes (1)

• organ dysfunctions

  Average variation in Pediatric Logistic Organ Dysfunction 2 ( PELOD-2) score compared between the IVIG treatment arm and the placebo arm.

  between day of admission and day 3

Secondary Outcomes (4)

• global mortality

  1 year

• 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

• organ dysfunctions assessed by the PELOD-2 score

  over the first 5 days in Paediatric Intensive Care Unit (PICU)

Study Arms (2)

IVIG

EXPERIMENTAL

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

Drug: PRIVIGEN (CSL Behring)

control

PLACEBO COMPARATOR

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.

Drug: Albumin

Interventions

PRIVIGEN (CSL Behring) DRUG

Single administration of intravenous immunoglobulin solution Privigen® (CSL Behring AG, Bern, Switzerland) at a dose of 2g / kg. IGIV 2g/kg within 12 hours following PICU admission (or outbreak of first shock signs). 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.

IVIG

Albumin DRUG

4%(LFB) ALBUMIN Single administration of human Albumin 4% diluted albumin (VIALEBEX® LFB), within 12 hours following PICU admission (or outbreak of first shock signs). Isovolume - so dose of 0.8 g/kg (4gG, 100 ML, Sodium chloride 0.61 G / 100ML Water for injections QSP 100 ML Sodium caprylate 0.3 G / 100ML) 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.

control

Eligibility Criteria

• Age: 1 Month - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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:
• Toxic Shock Syndrom as defined by Centre for Disease Control criteria
• or group A Streptococcus necrotizing fasciitis (positive streptest)
• or varicella with infected lesions and rash or positive streptest
• or erythrodermic rash in menstrual period
• or pleuropneumonia with erythrodermic rash or positive streptest in pleural fluid
• 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:
• hypotension (\< 5th percentile)
• or systolic blood pressure \< 2 SD regarding age
• 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)
• or 2 signs of hypo perfusion among:
• metabolic acidosis with base deficit \> 5
• lactate x 2 normal laboratory value

You may not qualify if:

• 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

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Hôpital Femme Mère Enfant

Bron, France

Location

MeSH Terms

Conditions

Staphylococcal Infections; Streptococcal Infections

Interventions

Immunoglobulins, Intravenous; Albumins

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Etienne JAVOUHEY

  Hospices Civils de Lyon

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2016
• First Posted: September 14, 2016
• Study Start: September 1, 2020
• Primary Completion: September 1, 2024
• Study Completion: September 1, 2024
• Last Updated: May 3, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)