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: 10459754
• 负责人: JULIO ALONSO CHIRINOS MEDINA
• 金额: $ 44.85万
• 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/10459754
• 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.

项目摘要 衰老、肥胖、糖尿病、高血压等危险因素与血脂和碳水化合物异常有关 代谢是2019冠状病毒病（COVID-19）死亡的风险因素。最近的研究表明， COVID-19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，其导致过量的细胞内脂质产生。此单元格中 培养系统，非诺贝特（一种由FDA批准的广泛可用的低成本仿制药和多种其他药物）， 世界各地的管理机构以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， 在COVID-19的背景下有益。 我们建议进行一项国际多中心随机安慰剂对照试验，以评估 非诺贝特对COVID-19患者预后的影响。我们将给予非诺贝特（145 mg/d的Tricor或剂量- 等效制剂，持续10天，在慢性肾病[CKD]中进行剂量调整）。我们 主要终点将是根据5个临床重要患者对患者结局进行排名的总体评分， 中心成果。分层终点实现了高统计功效，从而最大化了可能性 生产性II期试验，可以很容易地确定潜在的治疗进展到III期试验。我们将 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 利用与COVID-19的现有合作， 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NIH资助的 审判我们的建议有可能推进一种新的治疗（非诺贝特），一种广泛可用的，通用的， 一种廉价的药物，有着良好的安全记录。如果非诺贝特对COVID-19有效， 对COVID-19大流行产生重大公共卫生影响。