A multicenter, randomized, controlled, parallel-design trial evaluating Baricitinib in hospitalized patients with COVID19 pneumonia (COVID-BAR trial)
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 260
- 试验地点
- 3
- 主要终点
- Proportion of death or respiratory failure
研究概览
简要总结
Baricitinib is a selective reversible inhibitor of Janus kinases (JAK),approved for rheumatoid arthritis and recently received emergency useauthorisation (EUA) for COVID19. The progression of COVID19 frommoderate to severe disease is characterized by striking elevation of IL-6and other inflammatory markers. IL-6 signals via JAK1/2 receptors andactivates the intracellular STAT3 in T cells. Baricitinib potently inhibits thispathway and also blocks non-IL-6 pathways through TYK2/JAK1 that signalvarious other cytokines. It is also known to decrease viral entry into thetarget cells mediated by ACE2 receptor. In an unpublished report (COV-BARRIER trial), 1525 hospitalized adults with COVID-19 who were on highor low flow oxygen, but did not receive invasive mechanical ventilation,baricitinib was added to standard of care including steroids and remdesivir.The results showed non-significant difference in the primary endpointwhich was a composite of those who will progress to receiving high-flowoxygen, non-invasive and invasive ventilation and death at 28 days.However, there was a significant reduction in 28-day mortality. In thepreviously published landmark Adaptive COVID-19 Treatment Trial 2 (ACTT-2), baricitinib plus remdesivir reduced time to recovery compared withplacebo plus remdesivir. On the contrary, 29-day mortality was notstatistically significant with the addition of baricitinib to remdesivir. Twoobservational studies provide data on low dose and high dose baricitinib atdifferent time durations (2 mg and 8 mg respectively for 5 to 10 days and14 days respectively). The United States Food and Drug Administration (US-FDA) gave EUA to baricitinib in addition to remdesivir for COVID19 at thedose of 1 mg or 2 mg in steroid naïve patients while National Institute ofHealth (NIH) recommends use of baricitinib in COVID19 patients withpneumonia for up to 14 days or until hospital discharge whichever isearlier. Although Drug Controller General of India (DCGI) also gave EUA forits use, it is not clear on the dose, duration and its administration withcurrent standard of care i.e, steroids. Hence, we decided to conduct a trialevaluating the drug with current standard of care including remdesivir andsteroids and enrich data from India.
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •18 years and above of either sex Hospital admission within 10 days of RT-PCR positivity for COVID-19 SpO2 <94% at room air and require low flow oxygen support- through nasal canula, venturi mask or non-rebreather mask Normal procalcitonin- <0.4 ng/mL with no other evidence of any co- or secondary bacterial, viral or fungal infection at the time of randomization Considered to be an appropriate participant for intervention with an immunomodulatory in the opinion of the investigator Should be able to be maintained on venous thromboembolism prophylaxis or current maintenance therapy during inpatient dosing period, according to institutional protocol.
排除标准
- •Those who are on high flow oxygen or noninvasive or invasive mechanical ventilation or ECMO at the time of randomization Those on steroids for more than 10 days for any indication Patient has received baricitinib or any other immunomodulatory agent such as tumor necrosis factor [TNF] inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], T-cell or B-cell targeted therapies (rituximab), interferon, or Janus kinase (JAK) inhibitors for any indication within 4 weeks of the 1st dose of baricitinib Patient has inability to supply direct informed consent or if it was not possible to obtain from Next of Kin or Independent Healthcare Provider on behalf of patient Contraindications to study drugs, including history of hypersensitivity to the active substances or any of the excipients Suspected or known active infections including but not limited to tuberculosis, hepatitis B or C (no blood screening required), herpes zoster or HIV.
- •Current or past (within 3 months) participation in any interventional clinical trial including COVID-19-related disease trials (observational studies allowed) Patient moribund at presentation or screening or expected survival is <24h Pregnant or lactating women at screening (or unwillingness to adhere to pregnancy advice in protocol) Either alanine transaminase or aspartate transaminase (ALT or AST) > 5 times the upper limit of normal (ULN) Stage 4 severe chronic kidney disease or requiring dialysis (i.e. Cockcroft Gault estimated creatinine clearance < 30 ml /min) Currently receiving or ever received hyperimmune globulin, convalescent plasma or intravenous immunoglobulin [IVIg]) for COVID-19 Patient has received neutralizing antibodies, such as bamlanivimab-etesevimab, casirivimab-imdevimab and sotrovimab for COVID-
- •Patient has history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) within 12 weeks prior to randomization or has a history of recurrent (>1) VTE Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product Any medical history or clinically relevant abnormality that is deemed by the principal investigator and/or medical monitor to make the patient ineligible for inclusion because of a safety concern.
结局指标
主要结局
Proportion of death or respiratory failure
时间窗: Day 28
次要结局
- Proportion of respiratory failure(Day 14 and Day 28)
- Proportion of death(Day 14 and Day 28)
- Change in clinical status as assessed on NIAID 8-point ordinal scale compared to baseline(Day 28)
- Proportion of participants who require noninvasive ventilation(Day 14 and Day 28)
- Proportion of participants who require invasive ventilation(Day 14 and Day 28)
- Proportion of participants who require oxygen(Day 14 and Day 28)
- Duration of oxygen therapy(Day 180)
- Duration of noninvasive ventilation(Day 180)
- Time to clinical improvement(Day 180)
- Incidence of laboratory confirmed secondary fungal infections(Day 28 and Day 180)
- Duration of hospitalization(Day 180)
- Proportion of participants with adverse events of special interest in each treatment arm(Day 14, Day 28 and Day 180)
- Incidence of laboratory confirmed secondary bacterial infections(Day 28)
- Incidence of thrombotic events(Day 28)
- Duration of invasive ventilation(Day 180)
- Duration of ICU days(Day 180)
- Time to SpO2 94% on room air(Day 180)
- Percentage of Participants with a Change in Oxygen Saturation from 94% to ≥94% from(Baseline)