Efficacy of Montelukast in Mild-moderate Respiratory Symptoms in Patients With Long-COVID-19:

NCT ID: NCT04695704

Last Updated: 2024-07-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-11
• Study Completion Date: 2023-08-28

Brief Summary

Recently, a new clinical presentation called "long covid" has been reported, for patients with symptoms lasting for more than 4 weeks from the onset of the disease. Typically, the symptoms comprise dyspnea, cough, headache, arthralgia, fever, abdominal pain, asthenia and skin manifestations This project aims to evaluate the efficacy of Montelukast in improving the quality of life associated with respiratory symptoms in patients with persistent COVID-19 symptoms. The main objective is to compare the efficacy of low-dose Montelukast versus placebo to improve respiratory symptoms in patients with persistent COVID-19 symptoms.

Detailed Description

In December 2019, the first case of a new coronavirus causing pneumonia was described in Wuhan (China), designated as SARS-CoV-2 by the World Health Organization.

From the start of the SARS-CoV-2 alert until May 21st, 2020, 250,287 cases of coronavirus disease (COVID-19) were reported in Spain. The importance of the COVID-19 pandemic with its high humanitarian and economic cost, urgently requires effective therapies to reduce the severity, complications and mortality associated with this infection.

As the number of cases of COVID-19 increases, so does information regarding the management and evolution of the disease. More recently, a new clinical presentation called "long COVID-19" has been reported, for patients with symptoms lasting for more than 4 weeks from the onset of the disease. Typically, the symptoms comprise dyspnea, cough, headache, arthralgia, fever, abdominal pain, asthenia and skin manifestations.

The inflammatory process produced at the pulmonary and extra pulmonary level, and the immune response triggered have been identified as important mechanisms in the pathophysiology of COVID-19.

Coronavirus infection activates the cytokine cascade at the immune level, in which leukotriene are possibly involved in the development of respiratory symptoms in patients with persistent symptoms after infection by SARS-CoV-2.

Leukotriene antagonists (LTRAs) have a bronchodilator action and inhibit inflammation of the airways, resulting in a significant improvement in asthma symptoms and allergic rhinitis. In asthma, they improve respiratory function, inhalation rate of inhaled β2 agonist, airway inflammation, airway hyper responsiveness, inhaled corticosteroid dosage, and reduce exacerbations.

Regarding the treatment of acute SARS-CoV-2 infection, to date, the available evidence is limited; there are few conclusive clinical trials that allow recommendations based on scientific evidence.

To date, no treatment has been evaluated in long COVID-19. The hypothesis of using Montelukast would be based on the pathophysiological response of the disease mediated by the immune system against the SARS-CoV-2 infection.

Montelukast blocks the action of substances such as leukotriene C4, D4 and E4 by binding to the CysLT1 receptor in the lungs and bronchi. This reduces the bronchoconstriction caused by leukotriene and results in less inflammation.

Montelukast effectively attenuated both lung inflammation induced by Lipopolysaccharides in a mouse model with Acute Respiratory Distress Syndrome, as in human neutrophils.

Individuals affected by long COVID-19 have self-organized to gain visibility. They have made a self-completed form to describe the characteristics of the disease. The "Persistent COVID19" network in Catalonia currently gathers more than 3000 people.

From the contact with the "Persistent COVID19 association" in Catalonia, and in search of a response to this symptomatology, which can be very disabling, a pilot study was carried out in patients with persistent COVID-19 symptoms with off-label use of Montelukast.

Empirical treatment with Montelukast at a dose of 10 mg / day for 14 days was started in 13 patients with long COVID-19, some with symptoms of more than a month of evolution since the beginning of the COVID-19 clinic. The patients were followed up to evaluate the improvement of the symptoms with a numerical scale from 0 to 100 and COPD Assessment Test Scale (CAT), 3 weeks after starting treatment.

An improvement in symptoms was observed a few days after treatment and a good evolution of the sensation of dyspnea, chest pain, symptoms of discomfort, dry cough, and nasal symptoms. Likewise, the incorporation of the patients to their work activity during that period was observed. To date, the improvement continues to exist, without evidence of clinical deterioration.

Conditions

Covid19; SARS (Disease)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Montelukast

10mg oral montelukast once daily for 28 days.

Group Type: EXPERIMENTAL

Montelukast

Intervention Type: DRUG

10 mg oral montelukast once daily for 28 days

Placebo

oral placebo once daily for 28 days.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

10 mg oral placebo once daily for 28 days

Interventions

Montelukast

10 mg oral montelukast once daily for 28 days

Intervention Type: DRUG

placebo

10 mg oral placebo once daily for 28 days

Intervention Type: OTHER

Other Intervention Names

antileukotriene

Eligibility Criteria

Inclusion Criteria

• Patients 18 to 80 years old with SARS-CoV-2 infection (positive CRP <10 days from the onset of symptoms) treated in Primary Health Care.
• Persistent respiratory symptoms (more than 1 and <12 months of evolution)
• Mild-moderate dyspnea: score at the beginning of the study according to the modified Medical Research Council (mMRC) scale from 0 to 3
• The patient must be competent to complement the follow-up evaluations.
• The patient agrees to participate in the study and take assigned medication during the 4 weeks.
• Sign the informed consent

Exclusion Criteria

• Severity criteria: fever> 38ºC, or O2 saturation <93%.
• Patients with SARS-Cov-2 pneumonia in the acute / subacute phase.
• Patients who have required hospital admission for SARS-Cov-2.
• Chronic Obstructive Pulmonary Disease (COPD), asthma, bronchiectasis, pulmonary fibrosis, obstructive sleep apnea syndrome (OSAS), chronic respiratory failure from any cause, home oxygen therapy.
• Use of montelukast or zafirlukast ≤ 30 days prior to inclusion
• Use of any dose of systemic corticosteroids ≤ 30 days prior to inclusion
• Use of gemfibrocil.
• Hypersensitivity to montelukast or to any of the excipients included (e.g. lactose.
• Any condition (including the inability to swallow pills) that, in the opinion of the researcher, would prevent the completion of taking the medication.
• Active malignancy, current or recent chemotherapy treatment (<6 months).
• Medical history of infection by the Human Immunodeficiency Virus (HIV) or any serious immunocompromised state.
• Pregnancy, planning to get pregnant or patients of childbearing age not undergoing birth control methods.
• Breastfeeding mother.
• Any other condition for which, in the opinion of the principal investigator, it is considered that the subject does not fit the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Català de la Salut

OTHER

Sponsor Role: collaborator

Fundacio d'Investigacio en Atencio Primaria Jordi Gol i Gurina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jesus Almeda Ortega, PhD

Role: STUDY_CHAIR

Institut Català de la Salut

Sara Bonet Monne, PhD

Role: STUDY_CHAIR

Institut Català de la Salut

Betlem Salvador Gonzalez, PhD

Role: STUDY_CHAIR

Institut Català de la Salut

Francisco Mera Cordero, MD

Role: PRINCIPAL_INVESTIGATOR

Institut Català de la Salut

Locations

Primaty health Center Corbera

Corbera de Llobregat, Barcelona, Spain

Primary Health Center Jaume Soler

Cornellà de Llobregat, Barcelona, Spain

Primary Health Center 17 Setember

el Prat de Llobregat, Barcelona, Spain

Primary Health Center Camps Blancs

Sant Boi de Llobregat, Barcelona, Spain

Primary Health Center Molí Nou

Sant Boi de Llobregat, Barcelona, Spain

Primary Health Center Vinyets

Sant Boi de Llobregat, Barcelona, Spain

Primary Health Center ElPla

Sant Feliu de Llobregat, Barcelona, Spain

Primary Health Center Raval nord

Barcelona, , Spain

Countries

Spain

References

Mera-Cordero F, Bonet-Monne S, Almeda-Ortega J, Garcia-Sangenis A, Cunillera-Puertolas O, Contreras-Martos S, Alvarez-Munoz G, Monfa R, Balanzo-Joue M, Morros R, Salvador-Gonzalez B. Double-blind placebo-controlled randomized clinical trial to assess the efficacy of montelukast in mild to moderate respiratory symptoms of patients with long COVID: E-SPERANZA COVID Project study protocol. Trials. 2022 Jan 6;23(1):19. doi: 10.1186/s13063-021-05951-w.

Reference Type: DERIVED

PMID: 34991703 (View on PubMed)

Other Identifiers

4R21/006

Identifier Type: -

Identifier Source: org_study_id