Telmisartan in Respiratory Failure Due to COVID-19

COVID-19 Clinical Trial

— STAR-COVID  

Official title:

Effectiveness and Safety of Telmisartan in Acute Respiratory Failure Due to COVID-19

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04510662
• Other study ID #: CI/HRAEZ2020/05
• Status: Completed
• Phase: Phase 2
• Start date: August 12, 2020
• Est. completion date: May 25, 2021

Study information

• Verified date: October 2023
• Source: Hospital Regional de Alta Especialidad de Zumpango
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: May 25, 2021
• Est. primary completion date: May 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lung Injury
• COVID-19
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency
• Telmisartan

Intervention

Drug:
• Telmisartan
Patients in this group will receive telmisartan 40 mg daily plus standard care.

Locations

Country	Name	City	State
Mexico	Hospital Regional de Alta Especialidad de Zumpango	Zumpango	Estado De Mexico

Sponsors (2)

Lead Sponsor	Collaborator
Abraham Edgar Gracia-Ramos	National Polytechnic Institute, Mexico

Country where clinical trial is conducted

Mexico, 

References & Publications (5)

Bavishi C, Maddox TM, Messerli FH. Coronavirus Disease 2019 (COVID-19) Infection and Renin Angiotensin System Blockers. JAMA Cardiol. 2020 Jul 1;5(7):745-747. doi: 10.1001/jamacardio.2020.1282. No abstract available. — View Citation

Patel AB, Verma A. COVID-19 and Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: What Is the Evidence? JAMA. 2020 May 12;323(18):1769-1770. doi: 10.1001/jama.2020.4812. No abstract available. — View Citation

Rothlin RP, Vetulli HM, Duarte M, Pelorosso FG. Telmisartan as tentative angiotensin receptor blocker therapeutic for COVID-19. Drug Dev Res. 2020 Nov;81(7):768-770. doi: 10.1002/ddr.21679. Epub 2020 May 1. — View Citation

Sanchis-Gomar F, Lavie CJ, Perez-Quilis C, Henry BM, Lippi G. Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019. Mayo Clin Proc. 2020 Jun;95(6):1222-1230. doi: 10.1016/j.mayocp.2020.03.026. Epub 2020 Apr 4. — View Citation

Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med. 2020 Apr 23;382(17):1653-1659. doi: 10.1056/NEJMsr2005760. Epub 2020 Mar 30. No abstract available. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	Death is defined as all-cause mortality	Within 30 days
Primary	Mechanical ventilation	Occurrence of mechanical ventilation	Within 14 days
Secondary	Occurrence of acute kidney injury	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	Within 14 days
Secondary	Incidence of hypotension	Incidence of episodes of blood pressure less than 90 mm Hg systolic or 60 mm Hg diastolic	Within 14 days
Secondary	Incidence of hypotension requiring vasopressors	Outcome reported as the number of participants in each arm requiring the use of vasopressors for hypotension	Within 14 days
Secondary	Incidence of Sepsis	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	Within 14 days
Secondary	Hospital length of stay	Hospital length of stay (days)	Within 14 days