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The Covid-19 Outpatient Symptom Montelukast Oximetry Trial (COSMO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04389411
Recruitment Status : Not yet recruiting
First Posted : May 15, 2020
Last Update Posted : July 25, 2022
Sponsor:
Collaborators:
Segal Cancer Centre
The McGill Practice Based Research Network
Lady Davis Institute
Information provided by (Responsible Party):
Machelle Wilchesky, Lady Davis Institute

Brief Summary:
Primary care physicians face limited availability of therapeutic options for the treatment of COVID-19 in the outpatient setting. Furthermore, monoclonal antibodies and antiviral therapies that are currently approved for use in the outpatient setting by Health Canada have excluded pregnant women and older adults from their clinical trials, are contraindicated for many patients, and most are prohibited for use by pregnant women. Identification of a safe, COVID-19 outpatient therapeutic with 20-year safety record remains urgently needed.

Condition or disease Intervention/treatment Phase
COVID-19 Drug: Montelukast 10mg Phase 2 Phase 3

Detailed Description:

Objectives: Our overarching objective is to determine the efficacy of oral montelukast versus placebo in reducing the duration and severity of COVID-19 symptoms among newly infected at-risk adults in the outpatient setting using a randomized controlled trial. Our two primary objectives are to compare the efficacy of oral montelukast versus placebo in reducing:

  1. Symptom severity during the first 14 days of follow-up as measured by differences in mean FluPro PLUS scores and blood oxygen saturation SpO2 levels; and in reducing
  2. C-Reactive Protein a biomarker of inflammation associated with severe COVID, obtained on days 3, 6, 9, and 14 of follow-up.

Our 7 secondary objectives of the COSMO Trial include evaluating the efficacy of Montelukast in improving: i) Duration of symptoms; ii) Interleukin IL-6; iii) Hypoxemia; iv) Symptom severity during the first 21 and 30 days of follow-up; and v) Healthcare services use in the 6 months post infection (including MD visits).

Hypothesis & Preliminary Evidence: We hypothesize that repurposing Montelukast to target suppression of NF- KappaB activation in COVID-19 positive patients will result in a corresponding reduction of Pro-inflammatory mediators, thereby attenuating cytokine production, and taming the cytokine storm, improved blood oxygen saturation, a reduction in hypoxia, mitigation of severe COVID-19 symptoms, and serve as a therapeutic for SARS-CoV-2 infections. Published articles authored by Dr. Geoff Tranmer (study PI) and others provide details of this hypothesis. A retrospective analysis of 92 COVID-19 hospitalized patients conducted by our study collaborators in the USA and Belgium provides evidence that patients who had received montelukast experienced significantly fewer events of clinical deterioration compared to patients not receiving montelukast (10% vs 32%, p= 0.022). More compelling, however, is the fact that montelukast is presently being used by a growing number of clinicians around the world on a compassionate basis for their patients and is currently the standard for COVID-19 patient care in some parts of the world.

Methods and Approaches: The COvid-19 Symptom Montelukast Outpatient (COSMO) Trial will be a parallel assignment, phase II, quadruple blinded, randomized, placebo-controlled trial of Montelukast for the treatment of SARS-CoV-2 infections. The study will include 250 recently infected pregnant or older adult outpatients at risk of severe disease who will be randomized to receive either treatment (20mg oral Montelukast) or matched placebo once daily, for 21 to 30 consecutive days. Patient symptoms will be monitored daily for a period of 30 days, after which follow-up will continue for an additional 60 days for outcomes such as duration of symptoms, resilience, functional status, quality of life. Healthcare services use will be evaluated at 6 months post enrollment. The study will be conducted at the Segal Cancer Center and at Quebec Primary Care Medicine Clinics with the utilization of the McGill Primary Care Practice Based Research Network and the Segal Cancer Centre clinical trials infrastructure, with recruitment directly within participating clinics.

Expertise and Support: We have developed a team that possesses extensive clinical and epidemiology experience. To date, we have gained support from our participating clinics, the PRBN, the CEO of a CIUSSS Network, clinical trial infrastructure (Segal Centre), and clinical trial support (IMS). We have also received have in-kind support from Masimo (Rad-5/5V hand-held stand-alone hospital grade Pulse Oximeters valued at $40,000 CAD to be used for 3x daily symptom reporting) and $5,000USD in cash support from an independent partner.

Outcomes: A therapeutic will remain necessary in the context of uncertain vaccine effectiveness, vaccine hesitancy and viral mutations. With positive results from the COSMO trial, we expect Montelukast to be recommended for COVID-19 outpatients given that it is safe, effective, and globally available

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Montelukast and placebo tablets will be over encapsulated before distribution to trial participants.
Primary Purpose: Treatment
Official Title: Repurposing Montelukast for the Attenuation and Prophylaxis of Severe COVID-19 Symptoms: The COvid-19 Symptom MOntelukast (COSMO) Trial
Estimated Study Start Date : November 1, 2022
Estimated Primary Completion Date : January 2023
Estimated Study Completion Date : February 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Montelukast

Arm Intervention/treatment
Experimental: Montelukast
10mg Oral Montelukast once daily for 60 days
Drug: Montelukast 10mg
10mg oral Montelukast will be taken daily for 60 days

Placebo Comparator: Placebo
Placebo.
Drug: Montelukast 10mg
10mg oral Montelukast will be taken daily for 60 days




Primary Outcome Measures :
  1. Symptom Severity [ Time Frame: 14 days ]
    Symptom severity during the first 14 days of follow-up as measured by differences in mean FluPro PLUS scores

  2. C-Reactive Protein [ Time Frame: 14 days ]
    C-Reactive Protein a biomarker of inflammation associated with severe COVID, obtained on days 3, 6, 9, and 14 of follow-up


Secondary Outcome Measures :
  1. Duration of symptoms [ Time Frame: 90 days ]
    Duration of symptoms as measured by differences in mean FluPro PLUS scores

  2. Interleukin IL-6 [ Time Frame: 14 days ]
    Interleukin IL-6, a biomarker of inflammation associated with severe COVID, obtained on days 3, 6, 9, and 14 of follow-up

  3. Hypoxemia incidence [ Time Frame: 30 days ]
    Each participant will be provided with a Health Canada approved Masimo Rad 5/V pulse Oximeter upon enrollment. home pulse oximetry (SpO2) recorded 3 times daily for the first 30 days of follow-up. Hypoxemia will be defied as SpO2 <92% on room air for >5 minutes.

  4. Hypoxemia [ Time Frame: 30 days ]
    Differences in the means using the 2 lowest (validated) SpO2 values per patient

  5. Functional Status [ Time Frame: 30 days ]
    As measured using the Post-COVID-19 Functional Status Scale

  6. Time to other serious COVID-19 complications [ Time Frame: 12 weeks ]
    Complications will be defined as a composite endpoint including pneumonia, ARDS sepsis/septic shock, cardiomyopathy or arrhythmia, acute kidney injury, and secondary bacterial infections.

  7. Hospitalization [ Time Frame: 6 months ]
    Hospital visits- (healthcare services use component)

  8. Medications [ Time Frame: 6 months ]
    Medication use- (healthcare services use component)

  9. Physician Visits [ Time Frame: 6 months ]
    Visits to primary care and specialists- (healthcare services use component)

  10. Cost-Effectiveness [ Time Frame: 6 months ]
    Comparison of healthcare services use costs



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Confirmed SARS-CoV-2 infection, defined as RT-PCR provincial laboratory confirmation;
  2. Time from patient reported first symptoms date of enrollment <7 days;
  3. Must be experiencing at least 1 COVID-19 symptom that is either continuing or increasing in severity
  4. Severe disease risk factor requirements: i) Age 18-49: ≥3 risk factors ; ii) Age 50-59: ≥2 risk factors; iii) Age 60-69: ≥1 risk factor; iv) Pregnant or Age 70+: No requirements
  5. Participants must agree to: i) Use assigned medication for a maximum of 60 days or until relief of symptoms; and ii) Complete the FLU-PRO PLUS and SpO2 daily diary and other study assessments during the course of follow-up.

Exclusion Criteria:

  1. Any hospitalization for COVID-19 symptoms or complications prior to randomization;
  2. Use of montelukast ≤ 30 days to screening;
  3. Any contraindication to montelukast; and
  4. Any condition (including the inability to swallow pills) which, in the opinion of the Principal Investigator, would prevent full participation in and compliance with the trial protocol, or would interfere with the evaluation of trial endpoints.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04389411


Contacts
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Contact: Machelle Wilchesky, PhD (514) 220-5555 machelle.wilchesky@mcgill.ca
Contact: Geoffrey Tranmer, PhD (204) 474-8358 geoffrey.tranmer@umanitoba.ca

Sponsors and Collaborators
McGill University
Segal Cancer Centre
The McGill Practice Based Research Network
Lady Davis Institute
Investigators
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Principal Investigator: Machelle Wilchesky, PhD Lady Davis Institute and McGill University
Principal Investigator: Geoffrey Tranmer, PhD University of Manitoba
Principal Investigator: Roland Grad, MDCM MSc FCFP Herzl Family Practice Centre and McGill University
Publications:
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Responsible Party: Machelle Wilchesky, Assistant Professor, Lady Davis Institute
ClinicalTrials.gov Identifier: NCT04389411    
Other Study ID Numbers: 443807
First Posted: May 15, 2020    Key Record Dates
Last Update Posted: July 25, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: COSMO Trial Data Governance Plan: We have designed the COSMO Trial to uphold the FAIR principles such that the research data derived will be Findable, Accessible, Interoperable, and Reusable. The raw data from this study, once removed of identifiers, will be posted to a public data sharing resource to allow the data to be used and understood by the wider scientific community. The precise platforms and open access data repositories will be determined once the data is ready, but candidate platforms include github and the Google COVID-19 data sharing platform.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame: We will make this data available within 12 months of completion of data collection.
Access Criteria: Undetermined.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Montelukast
Anti-Asthmatic Agents
Respiratory System Agents
Leukotriene Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP1A2 Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action