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.
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
Drug: Montelukast 10mg
10mg oral Montelukast will be taken daily for 60 days
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.
Machelle Wilchesky, PhD
(514) 220-5555
machelle.wilchesky@mcgill.ca
Geoffrey Tranmer, PhD
(204) 474-8358
geoffrey.tranmer@umanitoba.ca