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.

COVID-19已导致全球报告病例超过3.5亿例，死亡人数超过560万， 在美国有7200万例病例和> 90万例死亡。高效疫苗现已上市，并且是第一批 防线。然而，随着时间的推移，免疫力会减弱，并且在完全接种疫苗后会出现突破性感染 据报道，有人感染了病毒，特别是新的变种。2021年12月，两种新型口服抗病毒药物 Nirmatrelvir/ritonavir（NMV/r）和Molnupiravir（MPV）被授予紧急使用许可 (EUA)FDA批准用于治疗具有高风险的轻度至中度COVID-19早期症状患者， 进展为严重疾病。这些授权是根据有限的已公布数据授予的， 关于其相对有效性、在现实世界中的有效性以及 具体的高风险亚群体仍有待答复。迫切需要了解现实世界 这些药物的有效性，特别是在高风险和脆弱人群中，以及长期 治疗患者的临床结局。这些知识对于患者、提供者、支付者和 政策制定者，以确保它们只在适当的人群和情况下使用， 临床证据。为了解决这些关键的知识差距，我们提出了以下假设： 假设1：NMV/r或MPV治疗将与COVID-19的显著减少相关 老年人、合并症负担高的老年人、 和社会弱势群体。 假设2：我们假设NMV/r和MPV治疗将显著降低 1年内的后续住院、急诊和门诊就诊 恢复后。治疗还将与急性心肌梗死、中风、 肾功能下降和糖尿病，与倾向评分匹配的未经治疗的人相比。 我们将使用退伍军人事务部的COVID-19共享数据资源（VA ORDCOVID）， 包含广泛的人口统计学、临床、药理学、实验室、生命体征和临床结局 来自多个经验证来源的信息。我们将比较那些接受NMV/r或MPV治疗的患者， 倾向评分匹配的未治疗对照组，人口统计学、临床变量、 目前的疾病，地理位置，治疗时间，疫苗接种状态，从完成全面 接种过程和加强剂量施用。私家侦探巴特博士有丰富的经验 并分析了大型国家数据库，并在包括 新英格兰医学杂志，内科学年鉴，JAMA内科学，临床医学杂志 调查，自然医学和其他。他已经得到了IRB的批准，可以研究流行病学， VA人群中SARS-CoV-2感染的病史和临床结果。