telmisartan in respiratory failure due to covid-19

Conditions: COVID-19; Respiratory Insufficiency; Telmisartan; Respiratory Distress Syndrome, Adult

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.


Eligibility criteria:
inclusion criteria: * 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. exclusion criteria: * 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.

Keywords: covid-19 telmisartan respiratory failure respiratory distress syndrome, adult