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

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02899702

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Staphylococcal Infection Streptococcal Infection	Drug: PRIVIGEN (CSL Behring) Drug: Albumin	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Sep 1, 2020

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Sep 1, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

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

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)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Month to 17 Years

Sexes Eligible for Study:

All

Accepts 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:

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