As of April 8, Johns Hopkins reports 1,441,128 cases of coronavirus disease 2019 (COVID-19) worldwide. While the virus continues to spread rapidly in the United States and elsewhere, the World Health Organization (WHO) estimates that 80% of people with COVID-19 will recover on their own, without needing to be treated in a hospital.But in 20% of patients, the infections can get worse.
As the virus enters lung cells, it starts to replicate, destroying the cells, resulting in the most common complication of COVID-19, acute respiratory distress syndrome (ARDS). Because of this complication, ventilators have become the single most important piece of equipment in the fight to sustain these patients.
A compassionate use trial is currently enrolling COVID-19 patients with ARDS to evaluate both inhaled and intravenous treatment with a common anti-clotting drug, tissue plasminogen activator (TPA), an anticoagulant approved by the United States Food and Drug Administration (FDA) for treating ischemic thrombotic stroke.
The study is led by Christopher D. Barrett, MD, a senior surgical resident at Beth Israel Deaconess Medical Center (BIDMC) and a research fellow at MIT; Michael B. Yaffe, MD, PhD, an attending surgeon in the departments of Acute Care Surgery, Trauma, and Surgical Critical Care, and in Surgical Oncology at BIDMC; and colleagues. Patients selected for the trial will either be on ventilators or appear to need ventilation.
Researchers have long considered anticoagulants to reduce ARDS-induced death, but the treatment was never adopted or formally approved by the FDA. However, in this case, a subset of patients with COVID-induced ARDS has given new light to the possibility. According to Yaffe, these patients are aggressively clotting around their catheters and intravenous lines.
Data from cases in China and Italy indicate the development of marked aberrations in the blood-clotting process in people with severe COVID-19 illness. These patients seem to have microthrombi within the tiny blood vessels supplying the lung alveoli, keeping the capillaries from filling with blood and thereby preventing proper gas exchange. This results in drastic drops in blood oxygen levels.
TPA dissolves the clots, opening small blood vessels, and improving the ability of the lungs and other critical organs to function normally. The drug also prevents clots from blocking blood vessels in the kidney and heart that may lead to kidney and heart failure.
As next steps in this clinical trial, the researchers will identify biomarkers to help determine which patients are likely to respond to TPA as treatment for COVID-19 induced ARDs. the researchers hope to test TPA in 12 patients but will evaluate its effectiveness and safety after four patients. They will use a lower dose than typically prescribed for stroke or heart attack patients, and the drug will also be administered over a longer time period.
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. According to Barrett and Yaffe, since the announcement of this study on March 23rd, physicians from around the country have been contacting them about treating their acutely ill patients. Because TPA is an FDA-approved drug already being used for patients who have had heart attacks or strokes, physicians are permitted to prescribe it for off-label use.
According to Yaffe, patients with aggressive clotting will show the most benefit from TPA treatment, and this new trial will support this hypothesis. If so, the ready availability of the drug in every major hospital will make it possible to save many lives almost immediately.
