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

Effectiveness of Intravenous Immunoglobulins (IVIG) in Toxic Shock Syndromes in Children: a Multicentre European Randomized Controlled Trial

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.

Study Overview

• Status: Withdrawn
• Conditions: Staphylococcal Infection; Streptococcal Infection
• Intervention / Treatment: Drug: PRIVIGEN (CSL Behring); Drug: Albumin

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Bron, France
    • Hôpital Femme Mère Enfant

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: IVIG; PRIVIGEN (CSL Behring) NORMAL HUMAN IMMUNOGLOBULINS L-PROLINE, Water for injection	Drug: PRIVIGEN (CSL Behring); 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.
Placebo Comparator: control; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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)

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Etienne JAVOUHEY, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): September 1, 2024
• Study Completion (Anticipated): September 1, 2024

Study Registration Dates

• First Submitted: September 2, 2016
• First Submitted That Met QC Criteria: September 8, 2016
• First Posted (Estimate): September 14, 2016

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Shock; Sepsis; Infections; Communicable Diseases; Shock, Septic; Staphylococcal Infections; Streptococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Immunoglobulins, Intravenous
• Other Study ID Numbers: 69HCL16_0079

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No