Effectiveness of Intravenous Immunoglobulins (IVIG) in Toxic Shock Syndromes in Children: a Multicentre European Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- organ dysfunctions
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
IVIG
PRIVIGEN (CSL Behring) NORMAL HUMAN IMMUNOGLOBULINS L-PROLINE, Water for injection
干预措施: PRIVIGEN (CSL Behring) (Drug)
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.
干预措施: Albumin (Drug)
结局指标
主要结局
organ dysfunctions
时间窗: 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.
次要结局
- organ dysfunctions assessed by the PELOD-2 score(over the first 5 days in Paediatric Intensive Care Unit (PICU))
- 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)
- global mortality(1 year)