Telmisartan in Respiratory Failure Due to COVID-19
Status:
Recruiting
Trial end date:
2021-04-01
Target enrollment:
Participant gender:
Summary
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.