Effect of Montelukast Therapy on Clinical Course, Pulmonary Function, and Mortality in Patients With COVID-19

Summary

'Pandemic' is a medical term that has become a ubiquitous part of the global vocabulary over the last year. Although pandemics have occurred throughout human history, their sociocultural, economic, and psychological impact can leave lasting damage. In the current COVID-19 pandemic, more than 200 million confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported to date. While most people present with mild symptoms such as loss of taste and smell, sore throat, joint pain, and headache, it can cause serious morbidity and mortality, especially in individuals over 65 years of age and those with comorbidities .

Acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS) are among the main causes of morbidity and mortality in COVID-19. A contributing factor in the development of these clinical conditions is overproduction of proinflammatory cytokines, primarily tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8, and IL-1β. These cytokines cause increased leukocyte accumulation in the alveolar spaces and consequently an increase in reactive oxygen radicals and proteases, which inevitably leads to capillary endothelial damage and alveolar epithelial damage .

Montelukast is a potent cysteinyl leukotriene (cysLT) receptor antagonist with anti-inflammatory activity and has been proven to significantly suppress oxidative stress. Moreover, cysLTs also have an important role in the regulation of cytokine production. Administration of high doses of montelukast reduces IL-4, IL-5, and IL-13 production by T helper 2 cells . This effect makes it an important anti-inflammatory agent in the treatment of asthma. In addition, montelukast was shown to significantly inhibit bradykinin-induced tracheal smooth muscle contraction, thus supporting an interaction between bradykinin and leukotriene mediators .

In studies investigating the efficacy of cysLT for ARDS and MAS, montelukast was found to increase interferon gamma (IFN-γ) production and significant decrease the production of proinflammatory cytokines such as IL-1β, IL-6, and IL-8 in mice infected with respiratory syncytial virus. In another study, cysLT prevented neutrophil infiltration, lung inflammation, and oxidative stress and significantly decreased levels of TNF-α and IL-6 in both the lung parenchyma and bronchoalveolar lavage fluid in an animal model of ARDS induced by hemorrhagic shock.

In this study, the investigators aimed to investigate the effect of treatment with varying doses of montelukast as an adjunct to standard antiviral therapy on pulmonary function tests and clinical course in patients with COVID-19.

Conditions

• COVID-19 Pneumonia

Interventions

DRUG

Standart treatment group

Group 1 (n=60) received standard treatment in accordance with our national COVID-19 diagnosis and treatment guide.

DRUG

Montelukast sodium 10 mg treatment

Group 2 (n=60) received 10 mg/day oral montelukast in addition to standard treatment

DRUG

Montelukast sodium 20 mg treatment

Group 3 (n=60) were given 20 mg/day oral montelukast in addition to standard treatment.

Sponsors & Collaborators

• Bugra Kerget

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-10-22

Primary Completion

2021-12-22

Completion

2022-01-22

Countries

• Turkey (Türkiye)

Study Locations