Telmisartan in Respiratory Failure Due to COVID-19

• Status: Recruiting
• Trial end date: 2021-04-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Abraham Edgar Gracia-Ramos
• Collaborator: National Polytechnic Institute, Mexico
• Treatments: Telmisartan

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.