Telmisartan in Respiratory Failure Due to COVID-19 (STAR-COVID)

Abraham Edgar Gracia-Ramos

Status and phase

Completed

Phase 2

Conditions

COVID-19

Telmisartan

Respiratory Insufficiency

Respiratory Distress Syndrome, Adult

Treatments

Drug: Telmisartan

Study type

Interventional

Funder types

Other

Identifiers

NCT04510662

CI/HRAEZ2020/05

Details and patient eligibility

About

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.

Enrollment

66 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.