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

Sponsor

Jordi Gol i Gurina Foundation (Other)

Overall Status

Recruiting

CT.gov ID

NCT04695704

Collaborator

Institut Català de la Salut (Other)

284

Enrollment

Locations

Arms

Anticipated Duration (Months)

35.5

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Covid19 SARS (Disease)	Drug: Montelukast Other: placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

284 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Double-blind randomized placebo-controlled clinical trial,.Double-blind randomized placebo-controlled clinical trial,.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Quadruple (Participant, Care Provider, Investigator and Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Double-blind Randomized Clinical Trial, Placebo-controlled to Assess the Efficacy of Montelukast in Mild-moderate Respiratory Symptoms in Patients With Long-COVID-19: E-SPERANZA COVID-19 PROJECT

Actual Study Start Date :

Aug 1, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Aug 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Montelukast 10mg oral montelukast once daily for 28 days.	Drug: Montelukast 10 mg oral montelukast once daily for 28 days Other Names: antileukotriene
Placebo Comparator: Placebo oral placebo once daily for 28 days.	Other: placebo 10 mg oral placebo once daily for 28 days

Arm

Intervention/Treatment

Experimental: Montelukast

10mg oral montelukast once daily for 28 days.

Drug: Montelukast

10 mg oral montelukast once daily for 28 days

Other Names:

antileukotriene

Placebo Comparator: Placebo

oral placebo once daily for 28 days.

Other: placebo

10 mg oral placebo once daily for 28 days

Outcome Measures

Primary Outcome Measures

COP Assessment Test Scale (CAT) [7, 14, 21 and 28 days]
Quality of life of respiratory symptoms according to COPD Assessment Test (CAT The COPD Assessment Test (CAT) is a questionnaire for people with COPD, designed to measure the impact of COPD on a person's life, and how this changes over time.Quality of life of respiratory symptoms according to COPD Assessment Test (CAT). This is a validated self-administered scale to quantify and monitor the impact of COPD on well-being and daily life. It consists of 8 items (from 0 to 5 points), and a total score of 0-40 (0-9 mild, 10-20 moderate, 21-30 severe and 31-40 very severe), being higher scores worse outcome. A difference of 2 or more points in health status is considered clinically significant.

Secondary Outcome Measures

1min sit-to-stand test [14 and 28 days]
Exercise capacity: number of repetitions performed in the 1min sit-to-stand test
O2 desaturation [14 and 28 days]
O2 desaturation ≥ 4% with effort (1min sit-to-stand test)
Visual Analogical Scale (VAS) [7, 14, 21 and 28 days]
Symptoms evaluated using numeric Visual Analogical Scale (VAS): asthenia, headache, ageusia, anosmia, and rhinitis . It is numbered from 0-10, where 0 is the absence and 10 the greatest intensity, meaning higher scores worse outcome. The patient selects the number that best evaluates the intensity of the symptom.
All-cause mortality [7, 14, 21 and 28 days]
Mortality from any cause during the study
Number of visits to primary care [28 days]
Number of visits of any kind to primary health care settings (phone visit or face to face visit) during the study period.
Number of visits to the emergency room [28 days]
Number of visits to emergency room form primary health o hospital settings during the study period.
Number of hospital admissions. [28 days]
Number of hospital admissions during the study period.
Medication side effects [7, 14, 21 and 28 days]
Number and type of adverse reactions during the study period related to medication.
Days of sick leave [28 days]
Number of days of incapacity for work (sick leave) during the study period.
Factors of inflamatory and prothrombotic processes: D-Dimer, N-terminal prohormone of brain natriuretic peptide (NT Pro-BNP), C-reactive protenin and Antinuclear antibodies (ANA) [0 and 28 days]
To analyze wether the factors of inflamatory and prothrombotic processes (D-Dimer, Pro-BNP, C-reactive protein, and ANA) at the begining of the study are response predictors to the treatment.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Primaty health Center Corbera	Corbera De Llobregat	Barcelona	Spain	08757
2	Primary Health Center Jaume Soler	Cornellà De Llobregat	Barcelona	Spain	08940
3	Primary Health Center 17 Setember	El Prat De Llobregat	Barcelona	Spain	08820
4	Primary Health Center Camps Blancs	Sant Boi De Llobregat	Barcelona	Spain	08830
5	Primary Health Center Molí Nou	Sant Boi De Llobregat	Barcelona	Spain	08830
6	Primary Health Center Vinyets	Sant Boi De Llobregat	Barcelona	Spain	08830
7	Primary Health Center ElPla	Sant Feliu De Llobregat	Barcelona	Spain	08980
8	Primary Health Center Raval nord	Barcelona		Spain	08001