Old Drug, New Treatment?

Trial to assess anticlotting medication to treat COVID-19-related respiratory failure

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This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

While the majority of people with COVID-19 won’t require hospitalization, those who do are likely to seek medical help as a result of acute respiratory distress syndrome (ARDS), a severe lung injury common in patients with critical illnesses. At present, there is no effective treatment for ARDS other than supportive care with mechanical ventilation.

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A team of physician-scientists at Harvard Medical School and Beth Israel Deaconess Medical Center is now enrolling patients in a clinical trial to evaluate a common anticlotting drug for the treatment of COVID-19-positive patients with ARDS. The newly launched trial follows a special report the team published in the Journal of Trauma and Acute Care Surgery suggesting that the use of a drug called tPA (tissue plasminogen activator) could reduce deaths among patients with ARDS as a complication of COVID-19.

Epidemiological models predict that hundreds of thousands of Americans will require mechanical ventilation in the coming months as a result of the COVID-19 pandemic, far exceeding the number  currently available in the United States.

“As the global pandemic of COVID-19 begins to oversaturate the world's medical capacity to accommodate a surge of patients with ARDS, it’s critical we consider how existing therapies that are widely available may be of use in this unprecedented public health emergency,” said the special report’s lead author and clinical trial investigator, Christopher Barrett, HMS research fellow in surgery and a senior surgical resident at Beth Israel Deaconess.

“If effective and safe for the treatment of ARDS in patients with COVID-19, tPA could save lives by reducing recovery time and freeing up more ventilators for other patients in need.” 

A clot-dissolving protein naturally produced by the body, tPA was first approved by the U.S. Food and Drug Administration in 1987 for the treatment of heart attack and later approved for acute massive pulmonary embolism and acute ischemic stroke. Researchers have considered the use of anticoagulant drugs to reduce ARDS-induced death for two decades. Though the approach has never been widely adopted or formally FDA-approved, a clinical observation made about a subset of patients with COVID-19 induced ARDS made the idea seem newly relevant.

“We’re hearing anecdotally that a subset of patients with COVID-19 induced ARDS are clotting abnormally around their catheters and IV lines,” said senior author, Michael Yaffe, HMS instructor in surgery at Beth Israel Deaconess. “We suspect these patients with aggressive clotting will show the most benefit from tPA treatment, and this new clinical trial will reveal whether that’s the case.”

Led by Yaffe and Barrett, the tPA clinical trial is now open and enrolling patients with COVID-19 induced ARDS admitted to Beth Israel Deaconess. Next steps will include identifying biomarkers—measurable characteristics such as blood levels of clotting factors—to help more accurately determine which patients are most likely to respond to tPA as a treatment for ARDS, said Yaffe, who is also professor of biology and biological engineering at MIT.

The collaborative research was facilitated by Beth Israel Lahey Health COVID-19 Innovation Hub —an effort led by Gyongyi Szabo, HMS member of the faculty of medicine and chief academic officer at Beth Israel Deaconess, to address the emerging challenges related to the pandemic.

Also involved in the clinical trial are colleagues in the Beth Israel Deaconess Department of Anesthesia, Critical Care and Pain Medicine, including Shahzad Shaefi, HMS assistant professor of anaesthesia at Beth Israel Deaconess, and department chair Daniel Talmor, the Edward Lowenstein Professor of Anaesthesia at HMS and Beth Israel Deaconess.

Since the publication of the special report on March 23, Barrett and Yaffe have already heard from physicians across the country eager to try tPA for the treatment of COVID-19-induced ARDS. Because the medication is an FDA-approved drug already in widespread use for patients who have had heart attacks or strokes, doctors are permitted to prescribe it for off-label usage.

Adapted from a Beth Israel Deaconess news release.