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

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ClinicalTrials.gov Identifier: NCT04695704
Recruitment Status : Not yet recruiting
First Posted : January 5, 2021
Last Update Posted : March 8, 2021
Sponsor:
Collaborator:
Institut Català de la Salut
Information provided by (Responsible Party):
Jordi Gol i Gurina Foundation

Tracking Information
First Submitted Date  ICMJE January 4, 2021
First Posted Date  ICMJE January 5, 2021
Last Update Posted Date March 8, 2021
Estimated Study Start Date  ICMJE April 1, 2021
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 4, 2021)
COP Assessment Test Scale (CAT) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 4, 2021)
COP Assessment Test Scale (CAT) [ Time Frame: 7, 14, 21 and 28 days ]
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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2021)
  • 1min sit-to-stand test [ Time Frame: 14 and 28 days ]
    Exercise capacity: number of repetitions performed in the 1min sit-to-stand test
  • O2 desaturation [ Time Frame: 14 and 28 days ]
    O2 desaturation ≥ 4% with effort (1min sit-to-stand test)
  • Visual Analogical Scale (VAS) [ Time Frame: 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 [ Time Frame: 7, 14, 21 and 28 days ]
    Mortality from any cause during the study
  • Number of visits to primary care [ Time Frame: 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 [ Time Frame: 28 days ]
    Number of visits to emergency room form primary health o hospital settings during the study period.
  • Number of hospital admissions. [ Time Frame: 28 days ]
    Number of hospital admissions during the study period.
  • Medication side effects [ Time Frame: 7, 14, 21 and 28 days ]
    Number and type of adverse reactions during the study period related to medication.
  • Days of sick leave [ Time Frame: 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) [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 4, 2021)
  • 1min sit-to-stand test [ Time Frame: 14 and 28 days ]
    Exercise capacity: number of repetitions performed in the 1min sit-to-stand test
  • O2 desaturation [ Time Frame: 14 and 28 days ]
    O2 desaturation ≥ 4% with effort (1min sit-to-stand test)
  • Visual Analogical Scale (VAS) [ Time Frame: 7, 14, 21 and 28 days ]
    Symptoms evaluated using numeric Visual Analogical Scale (VAS): asthenia, headache, ageusia, anosmia, and rhinitis.
  • All-cause mortality [ Time Frame: 7, 14, 21 and 28 days ]
    Mortality from any cause during the study
  • Number of visits to primary care [ Time Frame: 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 [ Time Frame: 28 days ]
    Number of visits to emergency room form primary health o hospital settings during the study period.
  • Number of hospital admissions. [ Time Frame: 28 days ]
    Number of hospital admissions during the study period.
  • Medication side effects [ Time Frame: 7, 14, 21 and 28 days ]
    Number and type of adverse reactions during the study period related to medication.
  • Days of sick leave [ Time Frame: 28 days ]
    Number of days of incapacity for work (sick leave) during the study period.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy of Montelukast in Mild-moderate Respiratory Symptoms in Patients With Long-COVID-19:
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
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
Condition  ICMJE
  • Covid19
  • SARS (Disease)
Intervention  ICMJE
  • Drug: Montelukast
    10 mg oral montelukast once daily for 28 days
    Other Name: antileukotriene
  • Other: placebo
    10 mg oral placebo once daily for 28 days
Study Arms  ICMJE
  • Experimental: Montelukast
    10mg oral montelukast once daily for 28 days.
    Intervention: Drug: Montelukast
  • Placebo Comparator: Placebo
    oral placebo once daily for 28 days.
    Intervention: Other: placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: January 4, 2021)
284
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date March 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 <3 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Francisco M Mera Cordero, MD +34699942492 franmcor@hotmail.com
Contact: Rosa Morros Padro, PhD +34934824124 idiap@idiapjgol.org
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04695704
Other Study ID Numbers  ICMJE 4R21/006
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jordi Gol i Gurina Foundation
Study Sponsor  ICMJE Jordi Gol i Gurina Foundation
Collaborators  ICMJE Institut Català de la Salut
Investigators  ICMJE
Study Chair: Jesus Almeda Ortega, PhD Institut Català de la Salut
Study Chair: Sara Bonet Monne, PhD Institut Català de la Salut
Study Chair: Betlem Salvador Gonzalez, PhD Institut Català de la Salut
Principal Investigator: Francisco Mera Cordero, MD Institut Català de la Salut
PRS Account Jordi Gol i Gurina Foundation
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP