Host Response Mediators in Coronavirus (COVID-19) Infection - Is There a Protective Effect of Angiotensin II Type 1 Receptor Blockers (ARBs) on Outcomes of Coronavirus Infection?
试验速览
- 阶段
- 不适用
- 入组人数
- 500
- 试验地点
- 15
- 主要终点
- COVID-19 WHO ordinal scale
研究概览
简要总结
The coronavirus (COVID-19) pandemic continues to grow exponentially. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows angiotensin II receptor blockers (ARBs) limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19. We will therefore collect clinical chart data and test angiotensin II levels of patients who are admitted to ICU with COVID-19 to determine whether there is a correlation between taking ARBs and clinical outcomes in these patients.
Other blood biomarkers and clinical risk factors for COVID-19 have come to light in recent weeks. We include these in our observational analysis to help generate an understanding of COVID-19 presentation and blood biomarker characterization of disease.
详细描述
Purpose: To determine whether angiotensin II receptor blockers (ARBs) decrease severity or mortality in hospitalized COVID-19 infected adults.
Main Hypothesis: Modulation of ACE2 by ARBs decreases the need for hospitalization, severity (need for ventilation, vasopressors, extracorporeal membrane oxygenation or renal replacement therapy) or mortality of hospitalized COVID-19 infected adults.
Secondary Hypotheses:
- Plasma angiotensin I and II and other biomarker levels are associated with effectiveness of ARBs in hospitalized COVID-19 adults
- Modulation of ACE2 by angiotensin type I receptor blockers is associated with decreased rate of hospitalization for COVID-19
- In patients already on ARBs when they are hospitalized continuing ARBs is associated with decreased World Health Organization (WHO) COVID-19 ordinal outcome scale
Justification: The COVID-19 epidemic continues to grow exponentially affecting over 71,429 individuals with 1775 deaths (February 17, 2020), mostly in China but also in other countries. The population mortality rate is 2% (lower than SARS (10%) and MERS (36%) but is 10% in hospitalized and 24% in ICU-admitted COVID-19 patients in China. Recent data from China (not yet public domain) suggest ICU mortality is higher (J. Marshall personal communication). Interventions to date include quarantine, isolation and usual clinical care. There are no proven antiviral or host modulating interventions for COVID-19. Notably, critically ill COVID-19 patients have similar mortality rates as sepsis and acute respiratory distress syndrome. Cohort studies have shown that patients already on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) have lower sepsis mortality. Angiotensin II worsens lung injury in influenza models because ACE2 is downregulated in H1N1, H5N1, H7N9, and SARS viral infections leading to increased angiotensin II. Angiotensin II levels are increased in human influenza and are associated with influenza viral load, disease progression and mortality. Preliminary data shows ARBs limits lung injury in murine influenza H7N9, as well as viral titre and RNA. ARBs could limit viral titre and organ injury in COVID-19.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals over 18 years of age who have confirmed COVID-19 infection (according to local hospital or provincial laboratories clinically approved laboratory testing for COVID-19).
排除标准
- 未提供
结局指标
主要结局
COVID-19 WHO ordinal scale
时间窗: 14 days
次要结局
- ICU admission(29 days or less (may be discharged from critical care before day 28))
- Organ Dysfunction(14 days)
- 28-day mortality(29 days or less (may be discharged from critical care before day 28))
- Hospital/ICU length of stay(29 days or less (may be discharged before day 28))
研究者
Jim Russell
Study-Wide Principal Investigator
University of British Columbia