Effectiveness and Safety of Telmisartan in Acute Respiratory Failure Due to COVID-19
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 66
- 试验地点
- 1
- 主要终点
- Death
研究概览
简要总结
Rationale: The renin-angiotensin-aldosterone system (RAAS) dysregulation may play a central role in the pathophysiology of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection associated acute lung injury (ALI) / acute respiratory distress syndrome (ARDS). In the RAAS, Angiotensin I (Ang I) is converted to angiotensin II (Ang II) by angiotensin converting enzyme (ACE). Ang II mediates vasoconstrictive, pro-inflammatory and pro-oxidative effects through agonism at Ang II type 1 receptor (AT1R). ACE2 converts Ang II to angiotensin 1-7 (Ang1-7), which finally binds to Mas receptor (MasR) and mediates many beneficial actions, including vasodilation and anti-inflammatory, anti-oxidant and antiapoptotic effects. ACE2, a homologue of ACE, is an integral cell membrane protein with a catalytic domain on the extracellular surface exposed to vasoactive peptides. SARS-CoV-2 penetrates the cell through ACE2, and the increase of this receptor (due to the use of ACE inhibitors or angiotensin receptor blockers [ARBs]) may facilitate SARS-CoV-2 infection, which might increase the risk of developing severe and fatal SARS-CoV-2 infection. However, through upregulation of ACE2, ACE inhibitors/ARBs can exert anti-inflammatory and antioxidative effects, which may be beneficial in preventing ALI and ARDS.
Objective: To evaluate the effectiveness and safety of telmisartan in respiratory failure due to COVID-19.
Study design: This is an open label, phase 2 clinical trial. Study population: Adult hospitalized SARS-CoV-2-infected patients (n=60). Intervention: The active-treatment arm will receive telmisartan 40 mg daily and the control arm will receive standard care. Treatment duration will be 14 days or up to hospital discharge <14 days or occurrence of the primary endpoint if <14 days.
Main study endpoint: The primary study endpoint is the occurrence within 14 days of randomization of either: 1) Mechanical ventilation or 2) Death.
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
- •Age greater than or equal to 18 years of age.
- •Admitted to the Hospital Regional de Alta Especialidad de Zumpango.
- •Confirmed SARS-CoV-2 infection with either: positive laboratory test for SARS-CoV-2; or positive CT thorax diagnostic for SARS-CoV-2 infection according to the prevailing criteria.
- •Hypoxic respiratory failure: SpO2 ≤94% on room OR tachypnea (respiratory rate ≥22 breaths/min).
- •Randomization:
- •Within 24 hours of confirmed in-hospital SARS-CoV-2 infection diagnosis OR
- •within 24 hours of hospital admission in case of pre-hospital confirmed SARS-CoV-2 infection.
- •In case there is a lack of laboratory tests for SARS-CoV-2 in a potentially eligible patient, a positive laboratory test for SARS-CoV-2 will be no longer required. In that case, the potentially eligible patient needs to meet the prevailing criteria for the diagnosis of SARS-CoV-2 infection, such as typical abnormalities on pulmonary CT in the setting of high clinical suspicion of SARS-CoV-2 infection.
排除标准
- •Admitted to ICU prior to randomization.
- •Currently taking an an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin receptor blocker (ARB).
- •Use of other investigational drugs at the time of enrollment
- •Prior reaction or intolerance to an ARB; or severe intolerance to an ACEi, defined as angio-oedema requiring medical intervention.
- •Systolic blood pressure < 105 mmHg or diastolic blood pressure <65mmHg.
- •Potassium greater than 5.5 mEq/L within 4 weeks of study enrollment.
- •Estimated Glomerular Filtration Rate (eGFR) of < 30ml/min/1.73 m2 within 4 weeks of study initiation.
- •A known history of renal artery stenosis.
- •AST and/or ALT > 3 times the upper limit of normal within 4 weeks of study enrollment.
- •Severe liver dysfunction (Child-Pugh score C), biliary cirrhosis or cholestasis.
- •Severe volume depletion or severe acute kidney injury.
- •Inability to obtain informed consent.
- •Pregnancy or breastfeeding.
研究组 & 干预措施
Telmisartan
Patients in this group will receive telmisartan 40 mg daily plus standard care.
干预措施: Telmisartan (Drug)
结局指标
主要结局
Death
时间窗: Within 30 days
Death is defined as all-cause mortality
Mechanical ventilation
时间窗: Within 14 days
Occurrence of mechanical ventilation
次要结局
- Hospital length of stay(Within 14 days)
- Incidence of hypotension requiring vasopressors(Within 14 days)
- Incidence of hypotension(Within 14 days)
- Incidence of Sepsis(Within 14 days)
- Occurrence of acute kidney injury(Within 14 days)
研究者
Abraham Edgar Gracia-Ramos
Physician of the Department of Internal Medicine
Hospital Regional de Alta Especialidad de Zumpango