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.

项目摘要与异常脂质和碳水化合物相关的衰老，肥胖，糖尿病，高血压和其他危险因素代谢是2019年冠状病毒病（COVID-19）死亡的危险因素。最近的研究表明人类肺原发支气管上皮细胞的共同感染取决于代谢机制包括细胞代谢的明显变化，导致细胞内脂质产生过多。在这个单元格中培养系统，非诺贝特（一种由FDA批准的广泛可用的低成本通用药物，多个其他世界各地的监管机构以可以在临床上实现的浓度来治疗血脂异常）明显抑制了SARS-COV-2病毒复制。非诺贝特还具有可能是免疫调节作用在Covid-19的环境中有益。我们提出了一项国际多中心随机安慰剂对照试验，以评估在COVID-19患者的结局上进行非诺贝元素。我们将管理非诺贝特（145 mg/d的三角形或剂量 - 将测试等效制剂10天，并在慢性肾脏疾病[CKD]中进行剂量调整）。我们的主要终点将是一个全球分数，根据5个临床上重要的患者 - 中心成果。分层端点具有很高的统计能力，从而最大程度地提高了可能性生产性II期试验可以轻松识别潜在的疗法，以提高III期试验。我们将评估各种次要和探索性终点。最后，我们旨在巩固国际网络这可以快速在Covid-19中迅速执行II阶段试验，并利用与Covid-19建立的合作拉丁美洲的临床研究人员。该网络可以轻松执行此试验并支持其他NIH资助试验。我们的建议有可能进步一种新颖的疗法（Fenodobrate），这是一种广泛可用的，通用和廉价的药物具有可靠的安全记录。如果非诺贝特对19.19有效，我们的试验可以对19009年大流行有重大的公共卫生影响。