Confirmation of the Antiviral Effects of Midodrine Identified With a Gene Expression Signature-based Screening of Inluenza A Virus Infected Cells
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 79
- 试验地点
- 39
- 主要终点
- Comparison of viral replication kinetics between the 2 arms
研究概览
简要总结
Rationale:
Classical antiviral therapies target viral proteins and are consequently subject to resistance. To counteract this limitation, alternative strategies have been developed that target cellular factors. We hypothesized that such an approach could also be useful to identify broad-spectrum antivirals. The influenza A virus was used as a model for its viral diversity and because of the need to develop therapies against unpredictable viruses as recently underlined by the H1N1 pandemic. Gene-expression signature-based screening identified broadly effective influenza A antivirals. Midodrine showed great results in inhibiting viral growth and was the most suited to confirm its efficacy in vivo.
The main objective of the study is to assess the efficacy of midodrine taken at usual recommended dose (7.5mg/day) versus no treatment on viral replication kinetics of virus Influenza A.
Secondary objectives: evaluation of the number of patients with a normalized viral load 2, 3 5 and 7 days post-treatment; description of the anti-viral efficacy of midodrine defined as the delay to obtain a prolonged negativity of viral RNA; description of the tolerance of midodrine, evaluation of the clinical response to study treatment; evaluation of the dynamic of viral replication; analysis of the frequency of emergence of mutants and associated resistance.
Methods:
This is a multicenter, randomized, open-label study comparing patients aged 18 to 65 years infected by influenza A virus. Nasopharyngeal washing will be performed at day 0 (randomization), 2, 3, 5 to show the viral replication evolution.
161 patients will be randomized as follows :
- Arm 1 : Midodrine, 2.5 mg, 3 times a day
- Arm 2 : No treatment The recruitment is performed by general practitioners in the Lyon area.
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •men and women aged 18 to 65 years,
- •with no long-term illness,
- •presenting flu-like symptoms for less than 42 hours (nasal congestion, sore throat, muscle soreness, asthenia, headache, chills/sweating, fever...),
- •infection with influenza A virus confirmed with a quick diagnostic test,
- •outpatient care,
- •must provide signed and informed consent,
- •beneficiary of a health insurance.
排除标准
- •severe form of flu,
- •pregnant women or positive pregnancy test,
- •breastfeeding women,
- •women of childbearing-potential with no efficient contraceptive,
- •history of chronic respiratory disease : asthma or chronic obstructive pulmonary disease,
- •renal failure,
- •Raynaud's disease,
- •history of epilepsy, confusion, hallucinations or of psychoneurotic state,
- •patients with an increased cardiovascular risk (> 20% according to the Framingham scale) or with a cardiovascular history,
- •patients having a congestive heart failure, swollen legs or a posture hypotension,
- •patients who received a influenza vaccine for seasons 2011-2012 or 2012-2013,
- •known hypersensitivity to any component of the treatment,
- •topical use of nasal decongestant (except physiological serum),
- •use of steroids, immunosuppressive or antipsychotics drugs (including treatments for nausea),
- •use of indirect sympathomimetics drugs (ephedrine, methylphenidate, phenylephrine, pseudoephedrine),
- •use of dopaminergic ergot alkaloids (bromocriptine, cabergoline, lisuride, pergolide) or vasoconstrictor ergot alkaloids (dihydroergotamine, ergotamine, methylergométrine, methylsergide),
- •known hypertension treated or not,
- •history of bradycardia,
- •history of urinary retention,
- •severe cardiopathy,
- •acute angle-closure glaucoma,
- •severe obliterative vasculopathy,
- •vasospasm,
- •thyrotoxicosis,
- •pheochromocytoma,
- •history of angina pectoris,
- •use of guanethidine and related, iproniazide (non selective MAOIs), alpha-blockers and digitalis drugs
- •use of neuraminidase inhibitors: oseltamivir, zanamivir; and M2 proton-selective ion channel inhibitors: amantadine and rimantadine
研究组 & 干预措施
Midodrine
Midodrine 2.5 mg orally 3 times daily, 5 day-treatment.
干预措施: Gutron® treatment (Drug)
结局指标
主要结局
Comparison of viral replication kinetics between the 2 arms
时间窗: 7 days
Comparison of the viral load slopes for 7 days post-study treatment start. Viral load will be measured at day 0, 2, 3, 5, and 7
次要结局
- Percentage of patients with a normalized viral load(7 days)
- Duration and severity of flu symptoms(7 days)
- Frequency, duration and level of replication of the virus in nose samples(7 days)
- Viral resistance and decrease of sensitivity of collected strains(7 days)
- Tolerance of midodrine : incidence of adverse effects(7 days)