Study Confirms No Benefit to Taking Montelukast for COVID-19 Symptoms

Montelukast, commonly used to treat asthma and allergies, is one of five FDA-approved repurposed medications tested in ACTIV-6, a nationwide remote study


May 22, 2024 – A study led by the Duke Clinical Research Institute (DCRI) in partnership with Vanderbilt University found no symptomatic or clinical benefit in taking montelukast at a dosage of 10mg per day for 14 days for the treatment of mild-to-moderate COVID-19 symptoms.

Adrian Hernandez

“There was no evidence of improvement in the rate of sustained recovery in participants who took this dose of montelukast versus those who took a placebo,” said Adrian Hernandez, MD, MHS, the study’s administrative principal investigator and executive director of the DCRI.

Findings appear on medRxiv, a pre-publication server, and have been submitted to a peer-reviewed journal.

ACTIV-6—"The Randomized Trial to Evaluate Efficacy of Repurposed Medications”—is a nationwide, remote, double-blind study that has enrolled over 10,500 participants from across the United States to evaluate the potential benefits for treating mild-to-moderate COVID-19 with repurposed medications.

In ACTIV-6, researchers studied the rate of sustained recovery, defined as three days without COVID-19 symptoms. Taking 10mg of montelukast daily for 14 days did not shorten the time to sustained recovery. There was also no difference in relief of symptoms for participants taking montelukast compared to a placebo.

Montelukast was chosen for this study because previous evidence suggested that it may be able to reduce inflammation caused by the virus. This arm of the study was open from January 2023 – June 2023, and was made up of 1,250 participants.

ACTIV-6 aims to include participants from diverse backgrounds so that study results are applicable to everyone affected by COVID-19. Over half, 64 percent, of participants in the montelukast arm identified as Hispanic/Latino. This is a step forward from the previous arm, which had 46 percent Hispanic/Latino participants. Compared to the previous arm, participants enrolled in this arm were older with a median age of 54 years and with 58 percent of participants older than 50 years. The median age in the previous arm was 50 years old with approximately 49 percent of participants older than 50 years.

Susanna Naggie, MD DCRI

“The ACTIV-6 team remains committed to learning which repurposed medications can help treat mild to moderate COVID-19, and to sharing study results with participants, the public, and scientific community when they are available,” said Susanna Naggie, MD, MHS, the DCRI principal investigator overseeing the study’s clinical coordinating center.

Repurposed medications are those already approved by the U.S. Food and Drug Administration (FDA) for other medical indications. Montelukast is one of five FDA-approved repurposed medications tested in ACTIV-6. Montelukast is an oral medication commonly used to treat chronic asthma and seasonal allergy symptoms. It is not approved by the FDA to treat COVID-19 and should only be taken as prescribed or as part of a clinical trial.

In addition to Hernandez and Naggie, members of the ACTIV-6 Executive Committee include Stacey Adam, David Boulware, Sean Collins, Allison DeLong, Sarah Dunsmore, G. Michael Felker, George Hanna, Chris Lindsell, Matthew McCarthy, Russell Rothman, Elizabeth Shenkman, Thomas Stewart, Florence Thicklin, and Rhonda Wilder.

ACTIV-6 ( identifier NCT04885530) received funding from the National Institutes of Health (3U24TR001608-06S1).

About ACTIV-6

ACTIV-6 is part of the National Institutes of Health-funded Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) and is led by the National Center for Advancing Translational Sciences (NCATS). The DCRI serves as the study’s clinical coordinating center, partnering with Vanderbilt University Medical Center as the study’s data coordinating center. The study is leveraging the infrastructure of PCORnet®, the National Patient-Centered Clinical Research Network, supported by the Patient-Centered Outcomes Research Institute, and the Trial Innovation Network, a collaborative initiative within the NCATS Clinical and Translational Science Awards Program that helps address critical roadblocks in clinical trials and accelerate the translation of novel interventions into life-saving therapies.

About the Duke Clinical Research Institute

The DCRI, part of the Duke University School of Medicine, is the largest academic clinical research organization in the world. Our mission is to develop, share, and implement knowledge that improves global health through innovative clinical research. The institute conducts multinational clinical trials, manages major national patient registries, and performs landmark outcomes research. The DCRI is a pioneer in cardiovascular and pediatric clinical research, and conducts groundbreaking clinical research across multiple other therapeutic areas, including infectious disease, neuroscience, respiratory medicine, and nephrology. The DCRI is also involved with other ACTIV studies, serving as the U.S. coordinating center for ACTIV-1, a COVID-19 master protocol study testing immune modulators, and participating in ACTIV-4, which is examining optimal use of oral anticoagulants to prevent COVID-19-associated blood clots.