A Randomized, Double Blind, Placebo Controlled Trial of Intravenous N-acetylcysteine and Oseltamivir Versus Intravenous 5% Dextrose and Oseltamivir in Adults Hospitalized With Influenza Complicated by Lower Respiratory Tract Infection.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Normalization of respiratory status in day
研究概览
简要总结
Seasonal influenza epidemics are important causes of morbidity and mortality. Cytokine dysregulation, with high levels of pro-inflammatory cytokines, occurs in patients with severe influenza. Early therapy with a neuraminidase inhibitor (NAI) is associated with better outcome in patients hospitalized with influenza, but significant mortality occurs despite use of antivirals. N-acetylcysteine (NAC) is a modified form of the amino acid cysteine, with anti-oxidant properties. NAC was shown to inhibit the production of pro-inflammatory molecules in lung epithelial cells infected with influenza viruses. Previous case report showed that high dose NAC, administered as continuous intravenous infusion, was effective and safe in improving the clinical outcomes. We aim to perform a randomized controlled trial to evaluate the therapeutic role of adjunctive NAC in the clinical management of patients with influenza complicated by lower respiratory tract involvement and abnormal respiratory status. Such information when available may reveal the potential of NAC for optimization of management of severe influenza, and provide important insights into future adjunctive therapy research.
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
- Triple (Participant, Care Provider, Outcomes Assessor)
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
- •influenza A and B virus infections confirmed by polymerase chain reaction (PCR) and/or immunofluorescence assays,
- •hospitalized for the management of severe manifestations of influenza,
- •initiation of oseltamivir,
- •clinical evidence of lower respiratory tract infection (e.g. shortness of breath, tachypnea, oxygen desaturation <93% on room air, crepitations on auscultation, infiltrations or consolidations on chest radiograph)
- •written informed consent (by the subjects, or from their next of kin if the subjects are unable to provide written consent at the time of enrollment)
排除标准
- •use of immunosuppressants (e.g. post-chemotherapy, post-transplant, autoimmune diseases) other than systemic corticosteroids
- •known immuno-compromised conditions (e.g. active haematological malignancies, HIV/AIDS patients who are on antiretroviral therapy and CD4 cell count < 200),
- •pregnancy
- •lactation,
- •end-stage renal failure
- •hepatic failure
- •cardiac failure
- •patients on anticoagulation (except prophylactic dose of low molecular weight heparin),
- •patients with scheduled major surgery within 2 weeks (NAC may affect blood clotting),
- •patients who have received macrolide antibiotics and NSAID for 1 week prior to enrolment due to their immuno-modulating effects.
- •Use of investigational anti-influenza antivirals and blood products
研究组 & 干预措施
intravenous N-acetylcysteine (NAC) and oseltamivir
干预措施: N-acetyl cysteine (Drug)
intravenous 5% dextrose and oseltamivir
干预措施: 5% Dextrose (Drug)
结局指标
主要结局
Normalization of respiratory status in day
时间窗: 28 days
oxygen saturation more than 93% or respiratory rate lower than 20/min on room air
次要结局
- interleukin 18 in pg/ml(10 days)
- phospho-p38 and phospho-ERK (activated MAPKs) in mean fluorescence intensity(MFI)(10 days)
- interleukin-8 in pg/ml(10 days)
- CRP in mg/L(10 days)
- Chemokine ligand 9 (CxCL9/MIG) in pg/ml(10 days)
- phospho-inhibitor kB/IkB (NF-kB) in mean fluorescence intensity(MFI)(10 days)
- mortality in days(28 days)
- viral ribonucleic acid (RNA) in copies per milliliter(28 days)
- Interleukin 6 in pg/ml(10 days)
- interleukin 17 in pg/ml(10 days)
- ICU admission in days(28 days)
- a six step ordinal scale of clinical status(7 days)
- Soluble tumour necrosis factor receptor-1 (sTNFR-1) in pg/ml(10 days)
- resolution of symptoms in days(28 days)
- Incidence of Treatment-Emergent Adverse Events in numbers(28 days)
研究者
Prof David Shu Cheong Hui
Professor
Chinese University of Hong Kong