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，死亡人数超过 560 万人，近 美国有 7200 万例病例和超过 90 万人死亡。高效疫苗现已问世，并且是第一个 防线。然而，免疫力会随着时间的推移而减弱，并且在完全接种疫苗的情况下会出现突破性感染 已有人报告，特别是较新的变种。 2021年12月，两种新型口服抗病毒药物 药物 Nirmatrelvir/ritonavir (NMV/r) 和 Molnupiravir (MPV) 获得紧急使用授权 (EUA) 被 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。这些授权是基于有限的已发布数据和关键的 关于它们的比较有效性、现实世界环境中的有效性以及在 具体的高风险亚人群仍有待解答。迫切需要了解现实世界 这些药物的有效性，特别是对高危和弱势人群，以及长期效果 治疗患者的临床结果。这些知识对于患者、提供者、支付者和 政策制定者，以确保它们仅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，我们提出以下假设： 假设 1：NMV/r 或 MPV 治疗将与 COVID-19 的显着减少相关 老年人、合并症负担较高的人的相关住院治疗和 30 天全因死亡率， 以及社会弱势群体。 假设 2：我们假设 NMV/r 和 MPV 治疗将与显着降低 一年内的后续入院、急诊科就诊和门诊就诊 恢复后。治疗还可以降低急性心肌梗死、中风、 与倾向评分匹配的未治疗者相比，肾功能下降和糖尿病。 我们将使用退伍军人事务部的 COVID-19 共享数据资源 (VA ORDCOVID)，该资源 包含广泛的人口统计学、临床、药理学、实验室、生命体征和临床结果 来自多个经过验证的来源的信息。我们将比较那些接受 NMV/r 或 MPV 治疗的患者 倾向评分与未治疗的对照相匹配，与人口统计、临床变量、严重程度相匹配 显示疾病、地理位置、治疗时间、疫苗接种状况、完成完整检查的时间 疫苗接种过程和加强剂量管理。 PI，巴特博士在创造方面拥有丰富的经验 并分析大型国家数据库，并在期刊上发表了 45 篇有关 COVID-19 的论文，其中包括 新英格兰医学杂志、内科医学年鉴、JAMA 内科医学、临床杂志 调查、自然医学等。他已经获得IRB批准研究流行病学、自然 VA 人群中 SARS-CoV-2 感染史和临床结果。