Primary care physicians face limited availability of therapeutic options for thetreatment of COVID-19 in the outpatient setting. Furthermore, monoclonal antibodies andantiviral therapies that are currently approved for use in the outpatient setting byHealth 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 recordremains 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