The ECLA PHRI COLCOVID Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,279
- 试验地点
- 1
- 主要终点
- Composite outcome: New requirement for mechanical ventilation or death
研究概览
简要总结
The ECLA PHRI COLCOVID Trial is a simple, pragmatic randomized open controlled trial to test the effects of colchicine on moderate/high-risk hospitalized COVID-19 patients with the aim of reducing mortality and/or new requirement for mechanical ventilation.
详细描述
Various anti-viral treatments are being tested in clinical trials worldwide. The World Health Organization (WHO) launched a simple,pragmatic worldwide open-label trial to test Remdesivir, Lopinavir/Ritonavir, Interferon and Hydroxychloroquine or Chloroquine.The most important complication of COVID-19 severe cases is respiratory failure from severe acute respiratory syndrome (SARS), the leading cause of mortality. Accumulating evidence suggests that patients with severe COVID-19 might have a cytokine storm syndrome, a hyperinflammatory syndrome characterized by a fulminant and fatal hypercytokinemia and multiorgan failure.
The proposed pathophysiological mechanism of cytokine storm and inflammatory cascade activation is based on evidence collected primarily during the SARS-CoV and MERS-CoV epidemics (with a significant increase in IL1B, IL6, IL12, IFNγ, IP10, TNFα, IL15, and IL17 among others). The data collected during the pandemic with COVID-19 also shows a significant increase in inflammatory cytokines (GCSF, IP10, MCP1, MIP1A, and TNFα, among others) in sicker patients admitted to intensive care. In the absence of effective treatments for the management of patients with COVID-19 and respiratory failure, the immunomodulatory and anti-inflammatory effect of colchicine on cytokines involved in the hyper-inflammatory state is postulated. Several lines of research worldwide are testing powerful anti-inflammatory drugs for the pandemic, with different options including steroids, cytokine blockers, and other potent anti-inflammatory agents. Steroids are partially contraindicated in viral infections.
Colchicine is a powerful anti-inflammatory drug approved for the treatment or prevention of gout and Familial Mediterranean Fever at doses ranging between 0.3 mg and 2.4 mg/day. Its mechanism of action is through the inhibition of tubulin polymerization, as well as through potential effects on cellular adhesion molecules and inflammatory chemokines. It might also have direct anti-inflammatory effects by inhibiting key inflammatory signalling networks known as inflammasome and pro-inflammatory cytokines. Additionally, evidence suggests that colchicine exerts a direct anti-inflammatory effect by inhibiting the synthesis of tumor necrosis factor alpha and IL-6, monocyte migration, and the secretion of matrix metalloproteinase-9. Through the disruption of the cytoskeleton, colchicine is believed to suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. All these are potentially beneficial effects that might diminish or ameliorate the COVID-19 inflammatory storm associated with severe forms of the disease. Importantly, in one contemporary trial low-dose colchicine administered to patients who survived from acute coronary syndrome shows a statistically significantly reduction of cardiovascular complications.
We have therefore designed in a simple, pragmatic randomized controlled trial to test the effects of colchicine on severe hospitalized COVID-19 cases with the aim of reducing mortality.
Sample size calculation:
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Local standard of care plus colchicine
Local standard of care plus colchicine (specific dosage schedule)
干预措施: Colchicine (Drug)
Local standard of care plus colchicine
Local standard of care plus colchicine (specific dosage schedule)
干预措施: Local standard of care (Other)
Local standard of care
Local standard of care for COVID-19 SARS moderate / high-risk patients
干预措施: Local standard of care (Other)
结局指标
主要结局
Composite outcome: New requirement for mechanical ventilation or death
时间窗: 28 days post randomization
Number of participants who require new intubation for mechanical ventilation or die
Mortality
时间窗: 28 days post randomization
Number of participants who die
次要结局
- New requirement for mechanical ventilation or death from non-respiratory failure(28 days post randomization)
- Highest WHO descriptive score of COVID-19 during hospitalization(During hospitalization or until death, whichever comes first, assessed up to 28 days)
- New requirement for mechanical ventilation or death from respiratory failure(28 days post randomization)
- Mortality due to respiratory failure(28 days post randomization)
- Mortality due to non-respiratory failure(28 days post randomization)
- In hospital - Composite outcome(During hospitalization or until death, whichever comes first, assessed up to 28 days)
- In hospital - Mortality(During hospitalization or until death, whichever comes first, assessed up to 28 days)
- Composite outcome (New requirement for mechanical ventilation or death) evaluated in Non-intubated population(28 days post randomization)
- Mortality evaluated in Non-intubated population(28 days post randomization)
- Mean WHO descriptive score of COVID-19 during hospitalization(During hospitalization or until death, whichever comes first, assessed up to 28 days)