BARICIVID-19 STUDY: MultiCentre, Randomised, Phase IIa Clinical Trial Evaluating Efficacy and Tolerability of Baricitinib as add-on Treatment of In-patients With COVID-19 Compared to Standard Therapy
试验速览
- 阶段
- 2 期
- 入组人数
- 126
- 试验地点
- 1
- 主要终点
- Need of invasive mechanical ventilation
研究概览
简要总结
There is urgent need of an effective therapy for Covid-19. To date, the best treatment of SARS-CoV-2 infection is unknown. Baricitinib has been identified as potential treatment for 2019-nCoV acute respiratory disease, because of its immunomodulating and hypothesized antiviral activity.
This is a multicenter randomized clinical trial that aims to evaluate the efficacy and safety of baricitinib in patients with SARS-CoV2 pneumonia. Patients will be randomized to receive or not baricitinib as adjunctive therapy. All patients will continue to receive the ongoing standard therapy: chloroquine/idrossichloroquine and low-molecular weight heparin (LMWH) eventually associated with ritonavir/lopinavir or darunavir/ritonavir will be allowed for all included patients.
The primary endpoint measure is the efficacy of baricitinib in reducing the number of patients requiring invasive ventilation after 7 and 14 days of treatment.
Secondary endpoints will be mortality rates and toxicity of baricitinib.
详细描述
There is urgent need of an effective therapy for Covid-19. To date, the best treatment of SARS-CoV-2 infection is unknown. Multiple strategies have been proposed and several randomized clinical trials are ongoing. Recently, data extracted from scientific literature by machine learning suggested a potential role of baricitinib, a Janus kinases (JAKs) inhibitor, that induces an anti-inflammatory effect and a dose dependent inhibition of IL-6. This drug is currently approved for the treatment of rheumatoid arthritis. However, it has been suggested that this drug may act against SARS-CoV-2 by inhibiting of the AP2-associated protein kinase 1 (AAK1), a regulator of the endocytosis pathway exploited by SARS-CoV-2 to infect lung cells through binding with ACE2. Disruption of AAK1 might interrupt the passage of the virus into cells and also the intracellular assembly of virus particles.
The aim of this study is to evaluate the efficacy and safety of baricitinib in patients with SARS-CoV2 pneumonia.
This is a multicenter randomized controlled clinical trial for evaluating efficacy, safety and tolerability of baricitinib added to the usual care treatments in comparison with the usual care treatments, enrolling patients with COVID-19 /SARS-CoV2 pneumonia.
The primary endpoint measure is the efficacy of baricitinib in reducing the number of patients requiring invasive ventilation after 7 and 14 days of treatment.
Secondary endpoints will be: mortality rate after 14- and 28-days from randomization; time to invasive mechanical ventilation (days); time to independence from non-invasive mechanical ventilation (days); time to independence from oxygen therapy (days); time to improvement in oxygenation for at least 48 hours (days); length of hospital stay (days); length of ICU stay (days); instrumental response (pulmonary echography); toxicity of baricitinib.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Any gender
- •Age > 18 years on day of signing informed consent
- •Informed written consent for participation in the study
- •Virological diagnosis of SARS-CoV-2 infection (real-time PCR)
- •Hospitalized due to clinical instrumental diagnosis of pneumonia.
- •Oxygen saturation at rest in ambient air ≤93% or P/F ratio <250
- •Able to be administered by oral route drugs
- •Patients who receive O2 therapy or who need non-invasive mechanical ventilation
- •In case of female patients at childbearing potential, they should agree to use highly effective methods of birth control at least till 7 days after the termination of the treatments
排除标准
- •Known hypersensitivity to Baricitinib or its excipients
- •Patients with Creatinine Clearance < 30 ml/min
- •Patients with active Tuberculosis (TBC)
- •Patients with known HBV or HCV infection
- •Patients with deep vein thrombosis (DVP) or Pulmonary Embolism (PE)
- •Patients with ALT or AST> 5 times the upper limit of the normality
- •Neutrophils <1000/mmc
- •Platelets <50.000/mmc
- •Hb< 8g/dl
- •Bowel diverticulitis or perforation
- •Patients who receive invasive mechanical ventilation
- •Documented bacterial infection at time of randomization
- •Patients with "do not resuscitate order"
- •Patients receiving immunosuppressants or anti-rejection drugs
- •Pregnancy or breastfeeding
研究组 & 干预措施
BAR group
Patients who will be assigned (after a computerized randomization) to the BAR group will. receive baricitinib as adjunctive therapy.
Baricitinib will be administered at 4 mg daily via oral route for 14 days as add-on therapy or 2 mg daily via oral route (eGFR between 30 and 60 ml/min and for patients with age >75 years old) for 14 days as add-on therapy
干预措施: Baricitinib Oral Tablet (Drug)
结局指标
主要结局
Need of invasive mechanical ventilation
时间窗: after 7 and 14 days of treatment
Reduction of the number of patients requiring invasive ventilation
次要结局
- Length of ICU stay(30 days)
- Proportion of adverse events(30 days)
- Mortality(14- and 28-days from randomization)
- Time to independence from oxygen therapy(30 days)
- Time to improvement in oxygenation for at least 48 hours(30 days)
- Length of hospital stay(30 days)
- Time to invasive mechanical ventilation(30 days)
- Time to independence from non-invasive mechanical ventilation(30 days)
- Instrumental response(30 days)
研究者
Francesco Menichetti
Professor
Azienda Ospedaliero, Universitaria Pisana