Impact of Colchicine on the Clinical Outcome of COVID-19 and the Development of Post-COVID-19 Pulmonary Fibrosis: Randomized Controlled Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 260
- 试验地点
- 1
- 主要终点
- Pulmonary fibrosis at week 2
研究概览
简要总结
Pulmonary fibrosis is a sequela to adult respiratory distress syndrome (ARDS). 40% of patients with corona virus disease 2019 (COVID-19) develop ARDS, and 20% of them are severe. Clinical, radiographic, and autopsy reports of pulmonary fibrosis were commonplace following SARS and MERS, and current evidence suggests pulmonary fibrosis could complicate infection by SARS-CoV-2 too. Colchicine has 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. It suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. All these are potentially beneficial effects that might diminish the COVID-19 inflammatory storm associated with severe cases.
详细描述
Approximately 96 million people have been diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and around two million people have died from this deadly disease worldwide. The pulmonary symptoms associated with SARS-CoV-2 vary from mild respiratory symptoms to severe respiratory failure. Of those infected with SARS-CoV-2, 40% will progress to ARDS.
Radiologically, most of those infected by SARS COV 2 have bilateral lower lobes ground-glass opacities with or without consolidation. However, long term lung impairment may develop particularly interstitial lung disease (ILD), the fibrotic type. Besides, pulmonary fibrosis (PF) is recognized sequelae of ARDS, and several studies have shown that protective lung ventilation tends to diminish the radiographic abnormalities following ARDS.
Colchicine has anti-fibrotic effects as a microtubule-destabilizing agent. In an in vitro study using human lung fibroblasts, colchicine inhibited myofibroblast differentiation via Rho/serum response factor (SRF) dependent. In COVID19 cases, colchicine was used by where they assessed its impact on the inflammatory biomarkers and clinical outcomes.
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
- Single (Outcomes Assessor)
盲法说明
The radiologist who will assess the CT scans will be blinded
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
- •Patients who are confirmed to have COVID-19 clinically, radiologically and PCR
- •Age above 18 years old
- •Informed written consent
排除标准
- •History of hypersensitivity to colchicine
- •Pregnancy or breastfeeding women.
- •Patients with severe renal impairment (creatinine clearance (CCL) <30 mL / min)
- •Patients with severe hepatic impairment (AST or ALT> 5 times the normal limits in International Units (ULN)
- •Patients with blood dyscrasias, neutrophils <1.000 / mmc or platelets <50.000 / mmc
- •Patients with history of severe cardiac insufficiency
- •Patients with history of pulmonary fibrosis
- •Severe diarrhoea or bowel diverticulitis, or perforation
- •Patients who cannot take oral therapy
- •Patients already in ICU or requiring mechanical ventilation
- •Patients already enrolled in other clinical trials
- •Patients with taking P-glycoprotein inhibitor (e.g. ciclosporin, verapamil or quinidine) or a CYP3A4 inhibitor (e.g. ritonavir, remdesivir, atazanavir, indinavir, clarithromycin, telithromycin, itraconazole or ketaconazole) or Tocilizumab
研究组 & 干预措施
Colchicine group
Colchicine 0.5 mg (2 tablets: 1 mg) twice per day as a loading dose, followed by one tablet 0.5 twice per day for three weeks in addition to the local standard protocol of COVID19 management
干预措施: the standard protocol only (Other)
Control group
the local standard protocol of COVID19 management
干预措施: the standard protocol only (Other)
Colchicine group
Colchicine 0.5 mg (2 tablets: 1 mg) twice per day as a loading dose, followed by one tablet 0.5 twice per day for three weeks in addition to the local standard protocol of COVID19 management
干预措施: Colchicine 0.5 MG (Drug)
结局指标
主要结局
Pulmonary fibrosis at week 2
时间窗: Two weeks
Percent of Participants with pulmonary fibrosis
Clinical status
时间窗: Two weeks
Seven-category ordinal scale: minimum 1 is the best and a maximum is 6
Pulmonary fibrosis at 45 days
时间窗: 45 days
Percent of Participants with pulmonary fibrosis
次要结局
- C-reactive protein(Two weeks)
- Erythrocyte sedimentation rate(Two weeks)
- Pulmonary function test: FVC(45 days)
- Adverse events(45 days)
- Ferritin(Two weeks)
- Pulmonary function test: FEV1(45 days)
- Lactate dehydrogenase(Two weeks)
研究者
Emad R Issak
Doctor
ClinAmygate