An Open Label Trial to Assess Safety of Losartan for Treating Worsening Respiratory Illness in COVID-19

Bengtson, Charles; Montgomery, Robert N.; Nazir, Usman; Satterwhite, Lewis; Kim, Michael D.; Bahr, Nathan C; Castro, Mario; Baumlin, Nathalie; Salathé, Matthias

doi:10.3389/fmed.2021.630209

Cited by 20 publications

(16 citation statements)

References 51 publications

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“…The study found that Losartan was safe for acute respiratory compromise caused by COVID-19. However, randomized trials are required to evaluate true efficacy [ 68 ].…”

Section: Emerging Therapies For Covid-19-induced Ardsmentioning

confidence: 99%

Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management

Aslan

Zolbanin

et al. 2021

Pneumonia

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COVID-19 pandemic is a serious concern in the new era. Acute respiratory distress syndrome (ARDS), and lung failure are the main lung diseases in COVID-19 patients. Even though COVID-19 vaccinations are available now, there is still an urgent need to find potential treatments to ease the effects of COVID-19 on already sick patients. Multiple experimental drugs have been approved by the FDA with unknown efficacy and possible adverse effects. Probably the increasing number of studies worldwide examining the potential COVID-19 related therapies will help to identification of effective ARDS treatment. In this review article, we first provide a summary on immunopathology of ARDS next we will give an overview of management of patients with COVID-19 requiring intensive care unit (ICU), while focusing on the current treatment strategies being evaluated in the clinical trials in COVID-19-induced ARDS patients.

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“…The study found that Losartan was safe for acute respiratory compromise caused by COVID-19. However, randomized trials are required to evaluate true efficacy [ 68 ].…”

Section: Emerging Therapies For Covid-19-induced Ardsmentioning

confidence: 99%

Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management

Aslan

Zolbanin

et al. 2021

Pneumonia

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“…The first, from University of Kansas, was a single-arm open-label trial assessing the ARB losartan in hospitalized COVID-19 patients requiring oxygen [13]. Thirty active treatment patients vs. 30 post-hoc external controls using propensity scores were compared, with the primary outcome being AE incidence.…”

Section: Discussionmentioning

confidence: 99%

COVID MED – An Early Pandemic Randomized Clinical Trial of Losartan for Hospitalized COVID-19 Patients

Freilich

Victory

Jenkins

et al. 2022

Preprint

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Background ACEi/ARB medications have been hypothesized to have potential benefit in COVID-19. Despite concern for increased ACE-2 expression in some animal models, preclinical and observational-retrospective and uncontrolled trials suggested possible benefit. Two RCTs of the ARB losartan from University of Minnesota showed no benefit yet safety signals for losartan in outpatient and hospitalized COVID-19 patients. COVID MED, started early in the pandemic, also assessed losartan in a RCT in hospitalized patients with COVID-19. Methods COVID MED was quadruple-blinded, placebo-controlled, multicenter randomized clinical trial (RCT). Hospitalized COVID-19 patients were randomized to receive standard care and hydroxychloroquine, lopinavir/ritonavir, losartan, or placebo. Hydroxychloroquine and lopinavir/ritonavir arms were discontinued after RCTs showed no benefit. We report data from the losartan arm compared to combined (lopinavir-ritonavir and placebo) and prespecified placebo-only controls. The primary endpoint was the NCOSS slope of change. Slow enrollment prompted early stopping. Results Of 432 screened patients, 14 were enrolled (3.5%), 9 received losartan and 5 combined control (lopinavir/ritonavir [N=2], placebo [N=3]); 1 hydroxychloroquine arm patient was excluded. Most baseline parameters were balanced. Treatment with losartan was not associated with a difference in NCOSS slope of change in comparison with combined control (p=0.4) or placebo-only control (p=0.05) (trend favoring placebo). 60-day mortality and overall AE and SAE rates were numerically but not significantly higher with losartan. Conclusions In this small blinded RCT in hospitalized COVID-19 patients, losartan did not improve outcome vs. control comparisons and was associated with adverse safety signals.

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“…Activation of the RAS system induces strong oxidative stresses that form the major pathogenic mechanism in COVID19 [ 120 ]. Losartan, being an angiotensin receptor 1 (AT1R) blocker in the RAS pathway, may be useful for COVID-19 patients who experience pneumonia [ 121 , 122 ]. Losartan appears to stimulate ACE2 overexpression and may increase viral entry.…”

Section: Potential Therapeutics For Management Of Covid-19mentioning

confidence: 99%

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

Kouhpayeh

Shariati

Boshtam

et al. 2021

IJMS

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In late 2019, a new member of the Coronaviridae family, officially designated as “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), emerged and spread rapidly. The Coronavirus Disease-19 (COVID-19) outbreak was accompanied by a high rate of morbidity and mortality worldwide and was declared a pandemic by the World Health Organization in March 2020. Within the Coronaviridae family, SARS-CoV-2 is considered to be the third most highly pathogenic virus that infects humans, following the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV). Four major mechanisms are thought to be involved in COVID-19 pathogenesis, including the activation of the renin-angiotensin system (RAS) signaling pathway, oxidative stress and cell death, cytokine storm, and endothelial dysfunction. Following virus entry and RAS activation, acute respiratory distress syndrome develops with an oxidative/nitrosative burst. The DNA damage induced by oxidative stress activates poly ADP-ribose polymerase-1 (PARP-1), viral macrodomain of non-structural protein 3, poly (ADP-ribose) glycohydrolase (PARG), and transient receptor potential melastatin type 2 (TRPM2) channel in a sequential manner which results in cell apoptosis or necrosis. In this review, blockers of angiotensin II receptor and/or PARP, PARG, and TRPM2, including vitamin D3, trehalose, tannins, flufenamic and mefenamic acid, and losartan, have been investigated for inhibiting RAS activation and quenching oxidative burst. Moreover, the application of organic and inorganic nanoparticles, including liposomes, dendrimers, quantum dots, and iron oxides, as therapeutic agents for SARS-CoV-2 were fully reviewed. In the present review, the clinical manifestations of COVID-19 are explained by focusing on molecular mechanisms. Potential therapeutic targets, including the RAS signaling pathway, PARP, PARG, and TRPM2, are also discussed in depth.

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An Open Label Trial to Assess Safety of Losartan for Treating Worsening Respiratory Illness in COVID-19

Cited by 20 publications

References 51 publications

Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management

Acute respiratory distress syndrome in COVID-19: possible mechanisms and therapeutic management

COVID MED – An Early Pandemic Randomized Clinical Trial of Losartan for Hospitalized COVID-19 Patients

The Molecular Basis of COVID-19 Pathogenesis, Conventional and Nanomedicine Therapy

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