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

Primary Purpose

Staphylococcal Infection, Streptococcal Infection

Status
Withdrawn
Phase
Phase 4
Locations
France
Study Type
Interventional
Intervention
PRIVIGEN (CSL Behring)
Albumin
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Staphylococcal Infection

Eligibility Criteria

1 Month - 17 Years (Child)All SexesDoes not accept 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

Sites / Locations

  • Hôpital Femme Mère Enfant

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

IVIG

control

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

global mortality
disability assessed by the Pediatric Overall Performance Category (POPC) score
impairment assessed by the Vineland Adaptive Behavior Scale 2 (VABS II)
organ dysfunctions assessed by the PELOD-2 score

Full Information

First Posted
September 2, 2016
Last Updated
April 28, 2021
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT02899702
Brief Title
Effectiveness of Intravenous Immunoglobulins (IVIG) in Toxic Shock Syndromes in Children
Acronym
IGHN2
Official Title
Effectiveness of Intravenous Immunoglobulins (IVIG) in Toxic Shock Syndromes in Children: a Multicentre European Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
April 2021
Overall Recruitment Status
Withdrawn
Why Stopped
no EC approval obtained
Study Start Date
September 2020 (Anticipated)
Primary Completion Date
September 2024 (Anticipated)
Study Completion Date
September 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Staphylococcal Infection, Streptococcal Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
IVIG
Arm Type
Experimental
Arm Description
PRIVIGEN (CSL Behring) NORMAL HUMAN IMMUNOGLOBULINS L-PROLINE, Water for injection
Arm Title
control
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
PRIVIGEN (CSL Behring)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Albumin
Intervention Description
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.
Primary Outcome Measure Information:
Title
organ dysfunctions
Description
Average variation in Pediatric Logistic Organ Dysfunction 2 ( PELOD-2) score compared between the IVIG treatment arm and the placebo arm.
Time Frame
between day of admission and day 3
Secondary Outcome Measure Information:
Title
global mortality
Time Frame
1 year
Title
disability assessed by the Pediatric Overall Performance Category (POPC) score
Time Frame
one year after recruitment
Title
impairment assessed by the Vineland Adaptive Behavior Scale 2 (VABS II)
Time Frame
one year after recruitment
Title
organ dysfunctions assessed by the PELOD-2 score
Time Frame
over the first 5 days in Paediatric Intensive Care Unit (PICU)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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: 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 diuresis < 0,5 ml/kg/h capillary refill time > 5 sec 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Etienne JAVOUHEY
Organizational Affiliation
Hospices Civils de Lyon
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Femme Mère Enfant
City
Bron
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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

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