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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要衰老、肥胖、糖尿病、高血压等与脂质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 (COVID-19) 死亡的危险因素。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着变化，导致细胞内脂质生成过多。在这个单元格中培养系统、非诺贝特（FDA 批准的一种广泛使用的低成本仿制药和多种其他药物）世界各地的监管机构以临床可达到的浓度治疗血脂异常，显着抑制 SARS-CoV-2 病毒复制。非诺贝特还具有免疫调节作用，可能是对于 COVID-19 的情况是有益的。我们提出一项国际多中心随机安慰剂对照试验来评估非诺贝特对 COVID-19 患者预后的影响。我们将给予非诺贝特（Tricor 145 毫克/天或剂量- 将测试 10 天的等效制剂，并调整慢性肾病 [CKD] 的剂量。我们的主要终点将是一个总体评分，根据 5 个临床重要的患者对患者结果进行排名以结果为中心。分层端点实现了高统计能力，从而最大化了可能性富有成效的 II 期试验，可以轻松识别进入 III 期试验的潜在疗法。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 的既定合作，可以快速执行 COVID-19 的 II 期试验拉丁美洲的临床研究人员。该网络可以轻松执行该试验并支持其他 NIH 资助的项目试验。我们的建议有可能推进一种新疗法（非诺贝特），一种广泛使用的、通用的和具有良好安全记录的廉价药物。如果非诺贝特对 COVID-19 有效，我们的试验可以对 COVID-19 大流行产生重大公共卫生影响。