The UPMC OPtimizing Treatment and Impact of Monocolonal antIbodieS Through Evaluation for COVID-19 Trial
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 发起方
- 入组人数
- 4,571
- 试验地点
- 2
- 主要终点
- Hospital-free Days
研究概览
简要总结
Multiple monoclonal antibodies (mABs) have been shown to reduce viral burden and improve clinical outcomes, have been granted FDA Emergency Use Authorization (EUA) for use in select populations, and are routinely used in the UPMC Health System, which has made expanded access a priority. However, the comparative effectiveness of these mABS is unknown. The National Academies of Sciences, Engineering, and Medicine has called for expanded access and clinical use of mABs, noting it is "critical to collect data and evaluate whether they are working as predicted". This pragmatic evaluation will determine the relative effects of the EUA-governed mABs versus each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mABs will accordingly change.
详细描述
While COVID-19 vaccination will reduce COVID-19-related morbidity and mortality, the learned immune response may vary between individuals. This means interventions such as monoclonal antibodies (mAB) will still be needed to prevent progression of COVID-19 illness. Monoclonal antibodies seek to mimic or enhance the natural immune system response against a pathogen and are often used in the care of patients with cancer or infection.
For viral infections, mABs are created by exposing a white blood cell to a particular viral protein, which is then cloned to mass produce antibodies to target that virus. For SARS-CoV-2, the virus that causes COVID-19, IgG1 mABs target the spike protein of SARS-CoV-2 and block viral attachment and entry into cells.
The SARS-CoV-2 mABs bamlanivimab and etesevimab, and the REGN-COV2 combination (casirivimab + imdevimab) reduce nasopharyngeal viral burden plus clinical outcomes including future emergency department visits and hospitalizations. Each received FDA Emergency Use Authorization (EUA) for use in selected populations.
As of February 2021, there are over 60,000 new cases of COVID-19 diagnosed daily in the US, with over 7000 daily COVID-19 related hospital admissions. Although case volumes are currently declining, COVID-19 remains a significant public health threat.
Despite the EUAs, the clinical use of mABs is low due in part to lack of patient access, complexities in drug allocation, and lack of knowledge among providers are contributing factors. Further, the comparative effectiveness of different mABs is unknown and not yet directly studied. The National Academies of Sciences, Engineering, and Medicine recently called for expanded access and clinical use of mABs, noting it is "critical to collect data and evaluate whether they are working as predicted". This evaluation seeks to determine their relative effects versus each other, starting with those governed by EUAs.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 120 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •COVID-19 positive patients
- •Eligible for mAB under FDA EUA
排除标准
- •Death is deemed to be imminent or inevitable
- •Previous participation in this REMAP within the last 90 days
结局指标
主要结局
Hospital-free Days
时间窗: 28 days after initial participation
Days alive and free from hospitalization. Patients that are both living and not in the hospital will meet criteria to be counted in this outcome. Deaths were rare and therefore the upper and lower end of the IQR are both 28, in addition to the median. This outcome measure does reflect median hospital free days and interquartile ranges for all groups.
次要结局
- SARS-CoV-2 Antibody Neutralization(28 days after initial participation)
- Detection of SARS-CoV-2 Variants Through Next-generation Sequencing(28 days after initial participation)
- Non-culture Surrogates for SARS-CoV-2 Infectivity(90 days after initial participation)
- ED Visit Within 28 Days(Duration of study)
- All-cause Mortality at 28 Days(28 days after initial participation)
- SARS-CoV-2 Nasopharyngeal Viral Loads(28 days after initial participation)
- Duration of SAR-CoV-2 Infectivity(90 days after initial participation)
- SARS-CoV-2 Plasma Viral Loads(28 days after initial participation)
- SARS-CoV-2 Antibody Titers(28 days after initial participation)
- SARS-CoV-2 Immune Responses(28 days after initial participation)
研究者
Erin McCreary
Clinical Assistant Professor
University of Pittsburgh Medical Center