Colchicine to Counteract Inflammatory Response in COVID-19 Pneumonia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 193
- 试验地点
- 1
- 主要终点
- Clinical improvement
研究概览
简要总结
Cytokines and chemokines are thought to play an important role in immunity and immunopathology during virus infections [3]. Patients with severe COVID-19 have higher serum levels of pro-inflammatory cytokines (TNF-α, IL-1 and IL-6) and chemokines (IL-8) compared to individuals with mild disease or healthy controls, similar to patients with SARS or MERS . The change of laboratory parameters, including elevated serum cytokine, chemokine levels, and increased NLR in infected patients are correlated with the severity of the disease and adverse outcome, suggesting a possible role for hyper-inflammatory responses in COVID-19 pathogenesis. Importantly, previous studies showed that viroporin E, a component of SARS-associated coronavirus (SARS-CoV), forms Ca2C-permeable ion channels and activates the NLRP3 inflammasome. In addition, another viroporin 3a was found to induce NLRP3 inflammasome activation . The mechanisms are unclear.
Colchicine, an old drug used in auto-inflammatory disorders (i.e., Familiar Mediterranean Fever and Bechet disease) and in gout, counteracts the assembly of the NLRP3 inflammasome, thereby reducing the release of IL-1b and an array of other interleukins, including IL-6, that are formed in response to danger signals. Recently, colchicine has been successfully used in two cases of life-threatening post-transplant capillary leak syndrome. These patients had required mechanically ventilation for weeks and hemodialysis, before receiving colchicine, which abruptly restored normal respiratory function and diuresis over 48 hrs [4].
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Positive nasopharyngeal swab for COVID-19, asymptomatic or paucisymptomatic, aged ≥70 years and/or with clinical risk factors for poor outcome (clinically relevant chronic lung disease, diabetes and/or heart disease) or
- •symptomatic with respiratory or systemic symptoms, however clinically stable (MEWS<3) with CT imaging showing viral pneumonia and positive or pending pharyngo-nasal swab for COVID-19: Temperature 38°C and/or intensive cough, Respiratory rate < 25 /min, oxygen saturation (pulse oximetry) >95%
- •Positive swab for COVID-19
- •with respiratory and/or systemic symptoms and initial mild respiratory failure e with objective signs of lung involvement; the patient is in stable conditions (MEWS < 3) Temperature>38°C and or intensive cough, Respiratory rate ≥25 /min, or oxygen saturation 94- 95% in room air
排除标准
- •Pregnant or breast feeding
- •MEWS >=3
- •Hepatic failure Child-Pugh C
- •Enrollment in other pharmacological studies
- •Ongoing treatment with colchicine
- •Ongoing treatment with antiviral drugs that include ritonavir or cobicistat
- •Any medical condition or disease which in the opinion of the Investigator may place the patient at unacceptable risk for study participation.
研究组 & 干预措施
Colchicine
Administration of Colchicine 1mg (or 0.5 mg in CKD)/day + standard of care for COVID-19 pneumonia
干预措施: Colchicine (Drug)
结局指标
主要结局
Clinical improvement
时间窗: Day 28
Time to clinical improvement: defined as time from randomization to an improvement of two points from the status at randomization on a seven-category ordinary scale
Hospital discharge
时间窗: Day 28
Live discharge from the hospital (whatever comes first)
次要结局
- Hospitalization(Day 28)
- Time from treatment initiation to death(Day 28)
- Death(Day 28)
- Clinical status(Day 7, Day 14)
- Mechanical ventilhation(Day 28)
- Time to Negativization COVID 19(Day 21)
- Fever(Day 1,4,7,14,21,28)
研究者
Umberto Maggiore
MD
Azienda Ospedaliero-Universitaria di Parma