Oral Antivirals against COVID-19 and Clinical Outcomes in High Risk Populations

针对 COVID-19 的口服抗病毒药物和高危人群的临床结果

• 批准号: 10574806
• 负责人: ADEEL A BUTT
• 金额: $ 15.78万
• 依托单位: VETERANS HEALTH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-12 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10574806
• 关键词: Acute myocardial infarction; Address; Affect; Ambulatory Care Facilities; Antiviral Agents; Authorization documentation; COVID-19; Cardiovascular system; Caring; Case Study; Cessation of life; Characteristics; Clinic Visits; Clinical; Collaborations; Communicable Diseases; Data; Databases; Diabetes Mellitus; Diagnosis; Disease; Disparity; Early treatment; Effectiveness; Elderly; Emergency Situation; Emergency department visit; Endocrine system; Event; FDA Emergency Use Authorization; Geographic Locations; Grant; Hepatic; Homelessness; Hospitalization; Immunity; Incidence; Institutional Review Boards; Internal Medicine; International; Journals; Kidney; Knowledge; Laboratories; Medical; Medicine; Mental disorders; Metabolic; Natural History; Nature; New Agents; New England; Oral; Outcome; Paper; Patients; Peer Review; Persons; Pharmaceutical Preparations; Policy Maker; Population; Poverty; Provider; Publications; Publishing; Recovery; Renal function; Reporting; Ritonavir; Role; SARS-CoV-2 infection; Severities; Source; Stroke; Therapeutic Agents; Time; United States Department of Veterans Affairs; United States Food and Drug Administration; Update; Vaccination; Vaccinee; Vaccines; Variant; Vulnerable Populations; authority; booster vaccine; breakthrough infection; clinical investigation; clinical practice; comorbidity; comparative effectiveness; data sharing networks; data warehouse; demographics; effectiveness evaluation; effectiveness study; epidemiology study; ethnic minority; evidence base; experience; gastrointestinal; health care service utilization; high risk; high risk population; molnupiravir; mortality; nirmatrelvir; novel; pharmacologic; physically handicapped; prevent; progression risk; public health emergency; racial minority; residence; respiratory; social vulnerability

COVID-19 has led to over 350 million reported cases and over 5.6 million resulting deaths globally, and nearly 72 million cases and >900,000 deaths in the US. Highly effective vaccines are now available and are the first line of defense. However, immunity wanes off over time and breakthrough infections in fully vaccinated persons have been reported, particularly with the newer variants. In December 2021, two novel oral antiviral agents, Nirmatrelvir/ritonavir (NMV/r) and Molnupiravir (MPV), were granted Emergency Use Authorization (EUA) by the FDA for treatment of early symptomatic patients with mild to moderate COVID-19 at high risk of progression to severe disease. These authorizations were granted based on limited published data, and critical questions about their comparative effectiveness, effectiveness in the real-world settings, and effectiveness in specific high-risk sub-populations remain to be answered. There is an urgent need to understand the real-world effectiveness of these drugs, especially in the high-risk and vulnerable populations, as well as longer term clinical outcomes in treated patients. Such knowledge is essential for the patients, providers, payors, and policymakers, to ensure that they are used only in the appropriate populations and situations based on strong clinical evidence. To address these critical gaps in knowledge, we propose the following hypotheses: Hypothesis 1: Treatment with NMV/r or MPV will be associated with a significant reduction in COVID-19 related hospitalization and 30-day all-cause mortality in older persons, those with a high comorbidity burden, and in socially vulnerable persons. Hypothesis 2: We hypothesize that NMV/r and MPV treatment will be associated with a significant reduction in subsequent hospital admissions, emergency department visits, and outpatient clinic visits over a 1-year period after recovery. Treatment will also be associated with a lower incidence of acute myocardial infarction, stroke, decline in renal function, and diabetes, compared with propensity-score matched untreated persons. We will use the Department of Veterans Affairs’ COVID-19 Shared Data Resource (VA ORDCOVID) which contains extensive demographic, clinical, pharmacologic, laboratory, vital signs and clinical outcomes information derived from multiple validated sources. We will compare those treated with NMV/r or MPV with propensity-score matched untreated controls, matched on demographics, clinical variables, severity of presenting illness, geographic location, time of treatment, vaccination status, time from completion of a full course of vaccination, and booster dose administration. The PI, Dr. Butt has extensive experience in creating and analysing large national databases and has published 45 papers on COVID-19 in journals including the New England Journal of Medicine, Annals of Internal Medicine, JAMA Internal Medicine, Journal of Clinical Investigation, Nature Medicine, and others. He already has IRB approval to study the epidemiology, natural history, and clinical outcomes of SARS-CoV-2 infection in the VA population.

新冠肺炎已导致全球超过3.5亿报告病例和560多万人死亡，近 在美国，7200万个病例和90万人死亡。高效疫苗现已问世，并是第一个 抢滩登陆Online。然而，免疫力随着时间的推移而减弱，在完全接种疫苗的情况下出现突破性感染 已有人被报告，特别是较新的变种。2021年12月，两种新型口服抗病毒药物 Nirmatrelvir/ritonavir(NMV/r)和Molnupiravir(MPV)获得紧急使用授权 (EUA)由食品和药物管理局用于治疗早期症状患者的轻中度新冠肺炎高风险 发展成严重的疾病。这些授权是基于有限的已发布数据授予的，并且 关于它们的相对有效性、在现实世界环境中的有效性以及在 具体的高危亚人群仍有待回答。我们迫切需要了解现实世界 这些药物的有效性，特别是在高危和脆弱人群以及较长期的 接受治疗的患者的临床结果。这些知识对于患者、提供者、付款人和 政策制定者，以确保它们只在适当的人群和情况下使用，基于强大的 临床证据。为了解决知识中的这些关键差距，我们提出了以下假设： 假设1：接受NMV/r或MPV治疗的患者新冠肺炎显著减少 老年人、高共病负担者的相关住院和30天全因死亡率， 以及在社会弱势群体中。 假设2：我们假设NMV/r和MPV治疗将与显著减少 一年内的后续住院、急诊科就诊和门诊就诊 在康复之后。治疗还将降低急性心肌梗死、中风、 肾功能下降和糖尿病，与倾向分数匹配的未经治疗的人相比。 我们将使用退伍军人事务部的新冠肺炎共享数据资源(VA ORDCOVID)，它 包含广泛的人口统计、临床、药理学、实验室、生命体征和临床结果 来自多个经过验证的来源的信息。我们会将NMV/r或MPV治疗的患者与 倾向-得分匹配的未经处理的对照组，在人口学、临床变量、严重程度上匹配 出现疾病、地理位置、治疗时间、疫苗接种状态、完成完全接种的时间 疫苗接种疗程和加强剂量管理。PI，Butt博士在创作方面拥有丰富的经验 并分析国家大型数据库，在新冠肺炎等期刊上发表论文45篇 《新英格兰医学杂志》、《内科年鉴》、《美国医学会内科杂志》、《临床杂志》 调查、自然医学和其他。他已经获得了IRB的批准，可以学习流行病学，自然 退伍军人中SARS-CoV-2感染的病史和临床结果。