Colchicine/Statins for the Prevention of COVID-19 Complications (COLSTAT) Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 250
- 试验地点
- 4
- 主要终点
- Number of Participants With COVID 19 Severity
研究概览
简要总结
This is a pragmatic randomized open-label study of the safety and efficacy of the combination of colchicine and Rosuvastatin in addition to standard of care (SOC) compared to SOC alone in hospitalized patients with SARS-CoV-2
详细描述
This is a prospective 1:1 randomized open-label clinical trial to investigate the safety and efficacy of the combination of Colchicine + Rosuvastatin added to standard of care (SOC) compared to SOC alone in hospitalized subjects with moderate COVID-19.
Subjects will be screened during admission to hospital. Patients with confirmed SARS-CoV-2 infection, and meeting all other inclusion and exclusion criteria, will be randomized to either Colchicine+Rosuvastatin treatment or SOC for the duration of hospitalization. SOC will be guided by the YNHH SARS-CoV-2 Therapeutics Group. In cases where patients require randomization in another trial evaluating an experimental drug, they will continue on study drug. Patients will be assessed daily while hospitalized for clinical, biomarker, safety, and laboratory parameters based on SOC.
Colchicine is an extensively studied oral anti-inflammatory agent with a well-defined safety profile. Colchicine, by inhibiting tubulin polymerization and clathrin-mediated endocytosis has the potential to inhibit SARS-CoV-2 cell entry. In addition, colchicine has a direct anti-inflammatory effect by inhibiting the NLRP3 inflammasome activation which in turn has the potential to reduce the SARS-CoV-2-induced cytokine storm. Statins also have direct anti-inflammatory effects by reducing chemokine release, adhesion molecules, and modulating T cell activity and have the potential to prevent SARS-CoV-2 related endothelial dysfunction and may reduce the morbidity and mortality associated with COVID-19. Rosuvastatin, in particular, appears to have direct antiviral properties by binding and inhibiting the active site of the main protease enzyme (Mpro) of SARS-CoV-2.1
The combination Colchicine + Rosuvastatin may have a synergetic effect to antagonize SARS-CoV-2 infection, modulate the inflammatory response and to reduce morbidity and mortality associated with acute respiratory distress syndrome (ARDS) and myocardial injury in COVID-19 patients.
Both drugs have been in use for decades for gout and pericarditis (colchicine) and hyperlipidemia, coronary disease (CAD) and diabetes (rosuvastatin/Crestor), and have been tested in thousands of patients used individually and in combination with a low and well characterized risk profile. Colchicine and rosuvastatin are currently used as standard of care in COVID-19 patients whether due to pre-existing CAD, gout or pericarditis or acute presentations with acute coronary syndromes or acute gout with no expected added risk in the population being studied.
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
- •Known pregnancy or nursing mothers
- •Known allergy to statins or colchicine
- •Patient is on chronic colchicine or oral corticosteroid treatment
- •Acute liver disease defined by elevated transaminases (AST/ALT > 3x ULN)
- •Severe chronic kidney disease defined as glomerular filtration rate (GFR) < 30mL/min1.73 m2
- •Severe QTc prolongation (>500ms narrow QRS<120ms and >550ms for wide QRS>120)
- •Presents with severe disease on admission (WHO ordinal scale of clinical improvement scores 5-8)
- •Rhabdomyolysis or CPK > 5x ULN
- •Thrombocytopenia defined as platelet count < 50,000 / mm3
- •Leukopenia defined as white blood cell count < 3000 ml
- •Severe anemia defined as Hemoglobin value <8 g/100ml
- •Participation in any other clinical trial of an experimental treatment for COVID-19
研究组 & 干预措施
Standard of Care (SOC) and Colchicine+Rosuvastatin
Patients will take Rosuvastatin 40mg daily and Colchicine 0.6mg twice for 3 days and then 0.6mg daily during hospitalization
干预措施: Standard of Care (SOC) and Colchicine+Rosuvastatin (Drug)
结局指标
主要结局
Number of Participants With COVID 19 Severity
时间窗: 30 Days
As defined by World Health Organization Ordinal Scale, which ranges from 1 to 8. Severity of COVID measured by WHO Scores 5-8: Defined as 5= Hospitalized requiring including CPAP, face mask, high flow nasal cannula (Excludes regular nasal cannula), 6= Hospitalized requiring intubation and mechanical ventilation, 7= Hospitalized requiring mechanical ventilation and additional organ support (vasopressors, renal replacement therapy, ECMO), 8= Death. Data presented is for Max WHO scores 5-8, indicating moderately to severely infected participants.
次要结局
未报告次要终点