Prevention of Chikungunya Infection in Neonates: Clinical Evaluation of Anti-CHIKV Hyperimmune Intravenous Immunoglobulins
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 40
- 试验地点
- 6
- 主要终点
- Safety
研究概览
简要总结
Chikungunya virus (CHIKV) has been detected in humans in the Caribbean area for the first time in November 2013 (St-Martin Island). By February 2014, the virus had spread to several other Caribbean islands as well as French Guyana, South America. During the outbreak of Chikungunya that affected the Reunion island in 2005/2006, it was observed that the neonatal forms of infections acquired by mother to child transmission during childbirth, were not the exception and were critical. Mother-to-child transmission occurs when the mother is viremic at the time of delivery. The mean duration of viremia after the onset of first clinical symptoms is six days. The rate of mother-to-child transmission is 50%. All neonates contaminated during labor and delivery present with a symptomatic disease and the rate of severe forms is about 50%, primarily due to damage of the central nervous system, often leaving permanent damage (seizures, cerebral palsy).Due to the severity of Chikungunya in neonates and the burden of cerebral palsy, it is imperative to identify a safe and effective preventive and/or curative intervention. Human polyvalent immunoglobulins purified from plasma samples obtained from Chikungunya-convalescent donors exhibit a potent neutralizing activity in vitro. They were evaluated for their preventive and curative effects in a neonatal mouse model of CHIKV infection. After administration of a lethal dose of CHIKV, all neonatal mice that had received immunoglobulins survived while all control animals that had received non hyperimmune immunoglobulins died. In humans, specific human immunoglobulins proved to be effective and safe in neonates born to hepatitis B viremic mothers.
Hypothesis : The investigators hypothesize that the administration of anti-CHIKV hyperimmune human intravenous immunoglobulins to neonates exposed to a high risk of severe form of Chikungunya infection is safe enough to justify its evaluation in an open non randomized trial aimed to confirm the safety and preliminary assess the efficacy of this intervention.
详细描述
The population to be studied will consist of neonates born to mothers presenting with clinical symptoms of Chikungunya within six days before and two days after childbirth. These neonates will therefore be exposed to a high risk of developing a severe form of Chikungunya infection. In most cases the reality of this risk will have been demonstrated by a positive CHIKV RT-PCR on maternal blood sampled before childbirth.
References to literature and data that are relevant to the trial, and that provide background for the trial.
Chikungunya virus has been detected in humans in the Caribbean area for the first time in November 2013 (St-Martin Island). By February 2014, the virus had spread to several other Caribbean islands as well as French Guyana, South America.
During the outbreak of Chikungunya (CHIK) that affected the Reunion Island in 2005/2006, the neonatal forms of infections acquired by mother-to-child transmission (MTCT) during childbirth, were reported in 50% of viremic mothers and associated with high neonate morbidity. MTCT occurred only when the mother was viremic at the time of delivery. The viremic period begins 2 days before the onset of symptoms and lasts for six days following the first symptoms. In infected neonates contaminated during labor, symptoms appeared after a median incubation period of 4 days. All neonate CHIK cases were symptomatic and the rate of severe forms was about 50%; these severe forms were primarily due to damages to the central nervous system, often leaving permanent damage (seizures, cerebral palsy).
Due to the severity of Chikungunya in neonates and the burden of cerebral palsy, it is imperative to identify a safe and effective preventive and/or curative intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 72 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Inclusion criteria in mothers:
- •Clinical symptoms consistent with CHIKV infection (acute-onset high-grade fever combined with bilateral polyarthralgia and no other cause than Chikungunya) during the pre-partum period or within the 48 hours post-partum,
- •Written informed consent obtained,
- •Negative Dengue fever rapid diagnostic test,
- •Blood sampled for CHIKV RT-PCR, processed in emergency, to be used to define 3 diagnosis categories at neonate's birth:
- •positive: definite maternal CHIKV infection,
- •pending: probable maternal CHIKV infection,
- •negative: maternal CHIKV infection excluded.
- •2. Inclusion criteria in neonates:
- •Neonate born to a mother fulfilling ALL maternal inclusion criteria and NO maternal
排除标准
- •Written informed consent signed by both neonate's parents (or legal guardians).
- •Exclusion Criteria:
- •1. Exclusion criteria in mothers:
- •Delivery more than 6 days after the onset of first symptoms of CHIKV infection,
- •Maternal CHIKV infection excluded,
- •Chronic active HBV infection (positive HBs Ag),
- •HIV infection.
- •2. Exclusion criteria in neonates:
- •Preterm neonate below 28 weeks of gestational age.
结局指标
主要结局
Safety
时间窗: 30 days
The primary endpoint will measure tolerability and safety of anti-CHIKV hyperimmune IVIG. It will be evaluated in all enrolled neonates and will be based on the occurrence of the following events: * patent ductus arteriosus, * ulceronecrotizing enterocolitis, * pulmonary hemorrhage, * tachycardia, hypotension, decreased O2 saturation during anti-CHIKV IVIG infusion, * hemolytic anemia, * fluid overload, as indicated by hyponatremia and/or ascites.
次要结局
- Efficacy(30 days)