UAB doctors hope a low-risk, FDA-approved drug to be tested at UAB Hospital will serve as a “rescue therapy” for ventilated patients with lungs seriously damaged by the coronavirus, COVID-19.
UAB is among the first in the nation to offer inhaled nitric oxide as a potential viable treatment in its intensive care unit for the sickest of these patients, officials said in a telephone news conference on April 8.
Nitric oxide is a colorless gas that is known to improve oxygen supply to injured tissues. It not only is used to help failing lungs, but it also exhibited antiviral effects against the SARS coronavirus during that 2003 epidemic. Since SARS is similar to the current pandemic infection, Dr. Pankaj Arora of UAB said hopes are that the same will be true with COVID-19.
Arora, assistant professor in UAB’s division of cardiovascular disease, will lead the UAB trial, part of an eight-center international effort that includes Harvard University/Massachusetts General Hospital and LSU Medical Center-Shreveport, three other centers in this country and two international centers.
UAB and Harvard have opened their trials and are recruiting patients, and LSU is nearing the start of its trial, Arora said in a news conference Wednesday.
At the centers, 200 patients will receive continuously inhaled nitric oxide in two high doses for a total of 72 hours. The dose will be 80 parts per million for the first 48 hours and 40 parts per million for the next 24 hours. After that, a patient’s attending physicians will determine whether it will be continued or not.
Listen to Dr. Pankaj Arora’s briefing on the trial
The trial’s primary end point is improvement in oxygenation after 48 hours. Researchers also will report on the mortality rate of enrolled patients as well as improvement in lung and heart function, and any improvement in ventilated perfusion of the lungs.
Eligible patients must have a confirmed diagnosis of COVID-19, be sick enough to be in intensive care unit and be breathing with the help of a ventilator, Arora said.
He and his colleague, cardiovascular disease research fellow Vibhu Parcha, said they expect recruitment to quickly fill the 200 slots. They also said Harvard, the principal site, will be expected to report results as they become available in increments of 25 patients to the Food and Drug Administration. The results are to be made available for doctors everywhere to analyze and decide how, or whether, to use the therapy.
“It’s all about generating robust medical data,” Parcha said. “We are here and trying to push it through, and given the severity of the disease, (results) could be out pretty soon. Since it’s a multicenter trial, we may reach the goal sooner than expected, but it’s difficult to put a time on it.”
Asked when they wanted the results, both physicians replied, “yesterday.” Parcha said, “We’re trying our best to reach the numbers the FDA is interested in. It’s all about generating robust medical data that the medical community can interpret and make conclusions about the therapy.”
Nitric Oxide Uses
Arora said that, in addition to studying the experimental treatment’s potential to rescue failing lungs, his group will study its cardiovascular effects. In its ability to boost oxygen to lung tissues, nitric oxide takes stress off the right side of the heart, which pumps blood to the lungs to pick up oxygen and dispense with carbon dioxide.
In humans, nitric oxide can regulate blood pressure, prevent formation of clots and destroy potential toxins, Arora said. Produced in blood vessels, it has been shown to protect against low oxygen in bodily tissues.
Nitric oxide relaxes and dilates the smooth muscles of blood vessels to increase their ability to transport oxygen. Physicians hope that its inhalation will treat acute respiratory distress syndrome, the major cause of death from COVID-19.
A mechanical ventilator pushes oxygen into the lungs at a set rate and force through a breathing tube. Patients are heavily sedated so they can’t fight the sensation of not being able to breathe on their own.
The gas has a sizeable history of successful use in newborns who have a heart defect that prevents the babies from getting sufficient oxygen.
The nitric oxide molecule is more widely known as the basis for treatment of erectile dysfunction. In 1992 it was named “molecule of the year” by Science magazine.
COVID-19 patients admitted to UAB’s intensive care unit and breathing with the assistance of a mechanical ventilator may qualify to be included in the trial. Parcha said the trial will serve as a “rescue therapy” to improve the status of the lungs.
Nitric oxide was called “a pretty remarkable drug” by Massachusetts General Hospital’s Dr. Lorenzo Berra, a critical care specialist who leads the international trial. “It has a risk profile that is minimal,” he told the Boston Herald.
Barra told the Herald the gas has been used in Italy for COVID-19 patients – albeit not in a controlled study – and appeared to significantly increase their oxygen levels. The new trial may help determine what would constitute optimal treatment, he said.
The drug is already FDA approved, so “widespread use could begin immediately,” according to Dr. Keith Scott, who leads the trial taking place at LSU-Shreveport.
Arora said UAB was able to join the trial quickly “due to collaborations across specialties and fields of expertise with the common goal of providing the highest quality of scientifically proven care for our COVID-19 patients.”
A proposed second trial now being reviewed at Massachusetts General Hospital would enroll health care workers who care for coronavirus patients to inhale a high dose of nitric oxide at the beginning and end of every shift.
UAB has been a hotbed of research into nitric oxide for decades. In the late 1970s while at the University of South Carolina, former faculty researcher Thomas Lincoln was the first to propose the mechanism behind the relaxation of blood vessels. Lincoln is now at the University of South Alabama. Nitric oxide became a major focus with the department of anesthesiology’s recruitment of top researchers, which led in the 1980s to the establishment of the UAB Center for Free Radical Biology.