Telmisartan for Treatment of COVID-19 Patients: an Open Label Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 400
- 试验地点
- 2
- 主要终点
- C reactive protein
研究概览
简要总结
In late 2019, a new coronavirus emerged in Wuhan Province, China, causing lung complications similar to those produced by the SARS coronavirus in the 2002-2003 epidemic. This new disease was named COVID-19 and the causative virus SARS-CoV-2. The SARS-CoV-2 virus, enters the airway and binds, by means of the S protein on its surface to the membrane protein ACE2 in type 2 alveolar cells. The S protein-ACE2 complex is internalized by endocytosis leading to a partial decrease or total loss of the enzymatic function ACE2 in the alveolar cells and in turn increasing the tissue concentration of pro-inflammatory angiotensin II by decreasing its degradation and reducing the concentration of its physiological antagonist angiotensin 1-7. High levels of angiotensin II on the lung interstitium can promote apoptosis initiating an inflammatory process with release of proinflammatory cytokines, establishing a self-powered cascade, leading eventually to ARDS. It has recently been proposed the tentative use of agents such as losartan and telmisartan as alternative options for treating COVID-19 patients prior to development of ARDS. The present study is an open-label randomized phase II clinical trial for the evaluation of telmisartan in COVID-19 patients. Briefly, patients with confirmed diagnosis of SARS-CoV-2, will be randomized to receive 80 mg/12h of telmisartan plus standard care or standard care alone aand will be monitored for development of systemic inflammation and acute respiratory distress syndrome. Other variables regarding lung function and cardiovascular function will also be evaluated.
详细描述
In late 2019, a new coronavirus emerged in Wuhan Province, China, causing lung complications similar to those produced by the SARS coronavirus (SARS-CoV) in the 2002-2003 epidemic. This new disease was named COVID-19 and the causative virus SARS-CoV-2 (Chen, Liu, & Guo, 2020; Li et al., 2020).
Given that vaccines against COVID-19 are still in development and an effective treatment against this new coronavirus is lacking, various pharmacological agents are being tested in clinical trials designed by institutions such as the WHO or scientific entities in different countries (C.-C. Lu, Chen, & Chang, 2020).
Taking into account the characteristics of the mode of entry of this coronavirus to human cells through binding with Angiotensin Converting Enzime 2 (ACE2) and extensive scientific and clinical evidence information on the Renin Angiotensin System, the hypothesis of the involvement of this system in the pathophysiology of COVID-19 was born (Gurwitz, 2020; Vaduganathan et al., 2020).
The SARS-CoV-2 virus, enters the airway and binds, by means of the S (Spike) protein on its surface (after whose image the term coronavirus is coined), to the membrane protein ACE2 in type 2 alveolar cells (R. Lu et al., 2020; Wan, Shang, Graham, Baric, & Li, 2020). The S protein-ACE2 complex is internalized by endocytosis and facilitates the entry of each virion into the cytoplasm. For each intracellular entry, the function of one ACE2 molecule is lost leading to a partial decrease or total loss of the enzymatic function ACE2 in the alveolar cells of the lung directly related to the viral load of the air inoculum.
ACE2 catalyzes the transformation of angiotensin II into angiotensin 1-7. Angiotensin II acting on AT1 receptors causes vasoconstriction, apoptosis, proinflammatory effects, and fibrosis. Angiotensin 1-7 acting on Mas receptors causes opposite effects: vasodilation and anti-inflammatory. Partial decrease or total loss of ACE2 function in alveolar cells results in a deviation of the homeostatic balance of the Renin Angiotensin System in favor of the angiotensin II-AT1 receptor axis (Paz Ocaranza et al., 2020; Tikellis, Bernardi, & Burns, 2011). Indeed, it increases the tissue concentration of angiotensin II by decreasing its degradation and reduces the concentration of its physiological antagonist angiotensin 1-7(Liu et al., 2020).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Aged 18 years or older
- •Confirmed diagnosis of COVID-19 by PCR test
- •Hospitalization for COVID-19
- •Illness symptoms beginning 4 days or less prior to randomization
排除标准
- •Admitted to ICU prior to randomization
- •Illness symptoms beginning more than 4 days prior to randomization
- •Pregnancy
- •Breast feeding
- •Major hypersensibility to angiotensin receptor blockers (ARBs)
- •Systolic blood pressure < 100mmHg
- •Potassium greater than 5.5 mEq/L
- •AST and/or ALT > 3 times the upper limit of normal
- •Serum creatinine higher than 3 mg/dL
- •Current treatment with angiotensin converting enzyme inhibitor (ACEi) or ARB
研究组 & 干预措施
TELMISARTAN
Patients in this group will receive 80 mg Telmisartan twice daily plus standard care.
干预措施: Telmisartan arm will receive 80 mg Telmisartan twice daily plus standard care. (Drug)
结局指标
主要结局
C reactive protein
时间窗: Days 5 and 8 after enrollment
Serum C rective protein levels
次要结局
- Occurrence of mechanical ventilation(Within 15 and 30 days after randomization)
- Admission to intensive care unit (ICU)(Within 15 and 30 days after randomization)
- Proportion of patients not requiring supplemental oxygen at day 15(Within 15 days)
- Composite occurrence of admission to ICU, mechanical ventilation or death (what occur first)(Within 15 and 30 days after randomization)
- Death(Within 15 days and 30 days)
- Time from randomization to discharge(Within 15 days)
- Significative differences in serum lactate dehydrogenase(Days 5 and 8)