Efficacy of Fenofibrate for COVID-19: A phase II randomized controlled trial

非诺贝特对 COVID-19 的疗效：II 期随机对照试验

• 批准号: 10245967
• 负责人: JULIO ALONSO CHIRINOS MEDINA
• 金额: $ 132.83万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10245967
• 关键词: 2019-nCoV; Adult Respiratory Distress Syndrome; Aging; Area Under Curve; COVID-19; COVID-19 mortality; COVID-19 pandemic; COVID-19 patient; Categories; Cause of Death; Cell Culture System; Cells; Cessation of life; Chronic Kidney Failure; Clinical; Clinical Trials Design; Clinical Trials Network; Collaborations; Data; Diabetes Mellitus; Dose; Dyslipidemias; Dyspnea; Economics; Enrollment; Epithelial Cells; Extracorporeal Membrane Oxygenation; FDA approved; Fenofibrate; Funding; Gene Expression Profiling; Generations; Generic Drugs; Geography; Hospitals; Human; Hypertension; Incidence; Intensive Care Units; International; Latin America; Lead; Lipids; Lung; Mechanical ventilation; Metabolic; Metabolism; Morbidity - disease rate; Nature; Nose; Obesity; Outcome; Outpatients; Oxygen; Oxygen Therapy Care; Participant; Patient Recruitments; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phase; Pneumonia; Preparation; Public Health; Randomized; Randomized Controlled Trials; Reporting; Research Personnel; Risk Factors; SARS-CoV-2 infection; SARS-CoV-2 inhibitor; Safety; Structure of parenchyma of lung; Symptoms; Testing; Time; United States National Institutes of Health; Virus; Virus Replication; appropriate dose; bronchial epithelium; carbohydrate metabolism; cost; design; immunoregulation; lipid metabolism; multi-site trial; novel therapeutics; phase II trial; phase III trial; primary endpoint; randomized placebo controlled trial; respiratory; secondary endpoint; supplemental oxygen

PROJECT SUMMARY Aging, obesity, diabetes, hypertension and other risk factors associated with abnormal lipid and carbohydrate metabolism are risk factors for death in Coronavirus disease 2019 (COVID-19). Recent studies suggest that COVID-19 infection of human lung primary bronchial epithelial cells is dependent on metabolic mechanisms including a marked shift in cellular metabolism that leads to excessive intracellular lipid generation. In this cell culture system, fenofibrate (a widely available low-cost generic drug approved by the FDA and multiple other regulatory agencies around the world to treat dyslipidemias) at concentrations that can be achieved clinically, markedly inhibited SARS-CoV-2 viral replication. Fenofibrate also has immunomodulatory effects that may be beneficial in the setting of COVID-19. We propose an international multicenter randomized placebo-controlled trial to assess the impact of fenofibrate on outcomes in patients with COVID-19. We will administer fenofibrate (145 mg/d of Tricor or dose- equivalent preparations for 10 days, with dose adjustment in chronic kidney disease [CKD]) will be tested. Our primary endpoint will be a global score that ranks patient outcomes according to 5 clinically important patient- centric outcomes. Out hierarchical endpoint achieves high statistical power and thus maximized the likelihood of productive phase II trials that can readily identify potential therapies for advance into phase III trials. We will assess various secondary and exploratory endpoints. Finally, we aim to consolidate an international network that can rapidly execute phase II trials in COVID-19, leveraging established collaborations with COVID-19 clinical researchers in Latin America. This network can readily execute this trial and support other NIH-funded trials. Our proposal has the potential to advance a novel therapy (fenofibrate), a widely available, generic and inexpensive drug with a proven track record of safety. If fenofibrate is effective for COVID-19, our trial could have a major public health impact on the COVID-19 pandemic.

项目总结 衰老、肥胖、糖尿病、高血压和其他与血脂和碳水化合物异常相关的危险因素 新陈代谢是2019年冠状病毒病死亡的风险因素(新冠肺炎)。最近的研究表明 新冠肺炎感染人肺原代支气管上皮细胞依赖于代谢机制 包括细胞代谢的显著变化，导致细胞内脂质生成过多。在这间牢房里 培养系统，非诺贝特(一种可广泛获得的低成本仿制药，由FDA和多家其他公司批准 世界各地的监管机构在临床上可以达到的浓度治疗血脂异常)， 显著抑制SARS-CoV-2病毒复制。非诺贝特还具有免疫调节作用，可能是 有益于新冠肺炎的设置。 我们建议一项国际多中心随机安慰剂对照试验来评估阿司匹林的影响 非诺贝特对新冠肺炎患者预后的影响。我们将使用非诺贝特(145毫克/天)或剂量- 10天的等量制剂，在慢性肾病[CKD]中进行剂量调整)将进行测试。我们的 主要终点将是根据5名临床重要患者对患者结果进行排名的全球评分- 以结果为中心。Out Hierarchy端点实现了高统计能力，从而最大化了可能性 能够很容易地确定进入第三阶段试验的潜在治疗方法的生产性第二阶段试验。我们会 评估各种次要和探索性终点。最后，我们的目标是巩固国际网络 可以利用与新冠肺炎建立的合作关系，在新冠肺炎快速执行第二阶段试验 拉丁美洲的临床研究人员。该网络可以随时执行这项试验，并支持其他由NIH资助的 审判。我们的建议有可能推进一种新的疗法(非诺贝特)，一种广泛可用的、仿制药和 价格低廉的药物，有经过证明的安全记录。如果非诺贝特对新冠肺炎有效，我们的试验可能 对新冠肺炎大流行有重大的公共卫生影响。