Telmisartan in Respiratory Failure Due to COVID-19

NCT04510662 | Completed Phase 2

• 1 other identifier: CI/HRAEZ2020/05
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

COVID-19; telmisartan; respiratory failure; respiratory distress syndrome, adult

Outcome Measures

Primary Outcomes (2)

• Death

  Death is defined as all-cause mortality

  Within 30 days

• Mechanical ventilation

  Occurrence of mechanical ventilation

  Within 14 days

Secondary Outcomes (5)

• Occurrence of acute kidney injury

  Within 14 days

• Incidence of hypotension

  Within 14 days

• Incidence of hypotension requiring vasopressors

  Within 14 days

• Incidence of Sepsis

  Within 14 days

• Hospital length of stay

  Within 14 days

Study Arms (2)

Telmisartan

EXPERIMENTAL

Patients in this group will receive telmisartan 40 mg daily plus standard care.

Drug: Telmisartan

Control

NO INTERVENTION

Patients in this group will receive standard care.

Interventions

Telmisartan DRUG

Patients in this group will receive telmisartan 40 mg daily plus standard care.

Telmisartan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Abraham Edgar Gracia-Ramos: lead
• National Polytechnic Institute, Mexico: collaborator

Study Sites (1)

Hospital Regional de Alta Especialidad de Zumpango

Zumpango, State of Mexico, 55600, Mexico

Location

Related Publications (5)

• 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.

  PMID: 32356926 BACKGROUND

• 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.

  PMID: 32376099 BACKGROUND

• 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.

  PMID: 32208485 BACKGROUND

• 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.

  PMID: 32242890 BACKGROUND

• 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.

  PMID: 32227760 BACKGROUND

MeSH Terms

Conditions

COVID-19; Respiratory Insufficiency; Respiratory Distress Syndrome

Interventions

Telmisartan

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Abraham Edgar Gracia-Ramos, MD MSc

  Hospital Regional de Alta Especialidad de Zumpango

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Physician of the Department of Internal Medicine

Study Record Dates

• First Submitted: August 11, 2020
• First Posted: August 12, 2020
• Study Start: August 12, 2020
• Primary Completion: May 15, 2021
• Study Completion: May 25, 2021
• Last Updated: October 5, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ME (1)