Early Interferon-beta Treatment for West-Nile Virus Infection
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Modified Rankin Scale (mRS) score
研究概览
简要总结
West Nile virus (WNV) is a mosquito-borne virus which in majority of cases causes only self-limited disease.
Despite that, in minority of cases (~0.5%) it can infect the brain and cause severe and even life-threatening disease (neuroinvasive disease).
Recent study has shown that up to 40% of WNV patients who develop neuroinvasive disease, have antibodies against Interferons (anti-Type I interferon autoantibodies), which neutralizes interferons, and could explain the development of severe disease.
The investigators therefore assume that early treatment with interferon beta (the type of interferon against which most patients do not have neutralizing antibodies) could prevent the development of severe neuroinvasive WNV disease.
详细描述
Scientific Background:
West Nile virus (WNV) is a mosquito-borne neurotropic flavivirus that can infect humans and cause life-threatening disease. In recent years, WNV infections have been reported in at least 60 countries across all continents, and is now a leading cause of mosquito-borne disease globally. While most infected individuals remain asymptomatic, around 20% develop a self-limited febrile illness, and less than 1% require hospitalization for neuro-invasive disease. These infrequent, yet severe, neurologic presentations can include encephalitis (50-70%), meningitis (15-35%), and acute flaccid paralysis (3-20%), which can result in a mortality of about 5-20%.
Epidemiologically, age is the strongest known predictor of neuroinvasive disease and death, and the risk of severe disease, particularly neuroinvasive disease, is about 16 times higher in those over the age of 65, and the risk of death is about 30-45 times higher in those over the age of 70.
One possible explanation for the higher risk of older patients to develop more severe disease, is the role of Type I interferons (IFNs) in mediating anti-WNV immunity. In-vitro studies using human cell lines and in-vivo murine models have shown that type-I IFNs can inhibit WNV replication in human cells and protect mice against lethal WNV infection. Even more compelling evidence for the role of type I IFNs in mediating anti-WNV immunity, is a case description of two WNV patients suffering neuroinvasive disease, who improved rapidly after initiation of IFNa treatment.
Accordingly, a recent study has identified very high prevalence of neutralizing anti-Type I IFN autoantibodies in patients with severe WNV neuroinvasive disease. Evaluating nearly 450 patients' samples, anti-Type I IFNs autoantibodies were identified in ~35% of WNV admitted patients and in 40% of those with neuroinvasive disease, including 31% of encephalitis cases, 46% of meningitis cases and 52% of cases of unspecified neurological syndrome. This is in comparison with a prevalence of only 3% in asymptomatic / mild WNV cases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Patients younger than 18 years old.
- •Pregnant women.
- •Contraindication for the administration of the drug: Hypersensitivity to natural or recombinant interferon beta, and decompensated liver disease.
- •A patient with neuroinvasive disease showing consistent spontaneous improvement over a period of > 2 days and mRS of below
- •More than 8 days from onset of neurological symptoms in immunocompetent patients and more than 10 days in immunocompromised patients. This time frame will be renewed if a patient with flaccid paralysis develops new onset encephalitis.
- •Patients who are receiving active chemotherapy treatment or suffer concurrent severe viral infection.
研究组 & 干预措施
Active Treatment
Patients enrolled to participate in the Active Treatment arm will receive 3 subcutaneous injections of 44mcg Interferon b-1a (Rebif), given 48h hours apart.
干预措施: Rebif 44 MCG Per 0.5 ML Prefilled Syringe (Drug)
Placebo
Patients enrolled to participate in the placebo arm will receive 3 subcutaneous injections of normal saline, given 48h hours apart.
干预措施: Saline (Drug)
结局指标
主要结局
Modified Rankin Scale (mRS) score
时间窗: 3 and 6 months
Comparison of modified Rankin Scale (mRS) score at 3 and 6 months. The mRS score is a 7 point (0-6) disability scale with higher score suggesting higher level of disability.
Rates of death or intubation
时间窗: 4 weeks
Death or intubation within 4 weeks
次要结局
- ICU admission(4 weeks)
- Modified-NIH-stroke-scale (mNIHSS)(3 months)
- All cause mortality(12 months)
- Mini-mental state examination (MMSE)(3 months)
- Mechanical ventilation(4 weeks)