The Covid-19 Outpatient Symptom Montelukast Oximetry Trial

NCT ID: NCT04389411

Last Updated: 2022-07-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-01
• Study Completion Date: 2025-02-28

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.

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

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Montelukast

10mg Oral Montelukast once daily for 60 days

Group Type: EXPERIMENTAL

Montelukast 10mg

Intervention Type: DRUG

10mg oral Montelukast will be taken daily for 60 days

Placebo

Placebo.

Group Type: PLACEBO_COMPARATOR

Montelukast 10mg

Intervention Type: DRUG

10mg oral Montelukast will be taken daily for 60 days

Interventions

Montelukast 10mg

10mg oral Montelukast will be taken daily for 60 days

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Segal Cancer Centre

UNKNOWN

Sponsor Role: collaborator

The McGill Practice Based Research Network

UNKNOWN

Sponsor Role: collaborator

Lady Davis Institute

OTHER

Sponsor Role: collaborator

McGill University

OTHER

Sponsor Role: lead

Responsible Party

Machelle Wilchesky

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Machelle Wilchesky, PhD

Role: PRINCIPAL_INVESTIGATOR

Lady Davis Institute and McGill University

Geoffrey Tranmer, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Roland Grad, MDCM MSc FCFP

Role: PRINCIPAL_INVESTIGATOR

Herzl Family Practice Centre and McGill University

Central Contacts

Machelle Wilchesky, PhD

Role: CONTACT

machelle.wilchesky@mcgill.ca

(514) 220-5555

Geoffrey Tranmer, PhD

Role: CONTACT

geoffrey.tranmer@umanitoba.ca

(204) 474-8358

References

Sanghai N, Tranmer GK. Taming the cytokine storm: repurposing montelukast for the attenuation and prophylaxis of severe COVID-19 symptoms. Drug Discov Today. 2020 Dec;25(12):2076-2079. doi: 10.1016/j.drudis.2020.09.013. Epub 2020 Sep 16.

Reference Type: BACKGROUND

PMID: 32949526 (View on PubMed)

Other Identifiers

443807

Identifier Type: -

Identifier Source: org_study_id