COVID-19, Respiratory Distress Syndrome, Adult, Respiratory Insufficiency, Telmisartan
Conditions
Keywords
COVID-19, telmisartan, respiratory failure, respiratory distress syndrome, adult
Brief 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.
Interventions
DRUGTelmisartan
Patients in this group will receive telmisartan 40 mg daily plus standard care.
Sponsors
National Polytechnic Institute, Mexico
Abraham Edgar Gracia-Ramos
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death | Within 30 days | Death is defined as all-cause mortality |
| Mechanical ventilation | Within 14 days | Occurrence of mechanical ventilation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of hypotension requiring vasopressors | Within 14 days | Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension |
| Occurrence of acute kidney injury | Within 14 days | Defined as a 50% decline in estimated glomerular filtration rate relative to baseline, or decrease of \>30 ml/min/1.73m2 and to a value below 60 ml/min/1.73m2 |
| Hospital length of stay | Within 14 days | Hospital length of stay (days) |
| Incidence of Sepsis | Within 14 days | Outcome reported as the number of participants in each arm who experience sepsis, defined as the presence of at least 2 of the following clinical criteria together (qSOFA score): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less |
| Incidence of hypotension | Within 14 days | Incidence of episodes of blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic |
Countries
Mexico
Outcome results
None listed