UW in trial for drug to stop deadly complication
Many COVID-19 deaths due to ‘cytokine storm’
The majority of people who die from COVID-19 are killed by a dangerous immune system overreaction called a cytokine storm, but researchers at the University of Wisconsin-Madison and dozens of other sites around the world are now testing a potential weapon against it.
UW announced Wednesday that it has joined the Phase III Clinical Trial of a drug known as ruxolitinib, becoming the 32nd site to begin recruiting patients. The drug is a government-approved medication given to bone marrow transplant recipients who are in danger of suffering a cytokine storm.
Cytokines are messengers that normally help the body’s immune system. But in a cytokine storm, far too many are released, and they wind up killing both healthy and diseased cells.
In COVID-19 patients, a cytokine storm can severely damage the lungs, kidneys and heart.
The ruxolitinib trial is UW’s third clinical trial of a potential treatment for COVID-19. The university is already participating in nationwide clinical trials using plasma from recovered COVID-19 patients to treat those still sick with the disease.
UW has also agreed to take part in a study of different treatments to prevent blood clots from forming in COVID-19 patients, though this trial has not yet started.
“We’ve been on the lookout for any promising therapy for this disease,” said David Andes, a UW professor of medicine specializing in infectious diseases, who will lead the Madison portion of the ruxolitinib trial.
Andes said he hopes to recruit up to 10 patients for the randomized, placebo-controlled trial — an approach considered the gold standard for scientific testing. Half the patients will receive ruxolitinib, while the other half will receive a sugar pill and supportive care, including ventilation and intravenous fluids.
Incyte, a pharmaceutical company based in Alapocas, Delaware, discovered the molecule ruxolitinib and is partnering on the clinical trials with the global health care company Novartis, headquartered in Basel, Switzerland. All told, the trial organizers expect to enroll 402 patients at 79 sites.
The trial is scheduled for completion in October.
Before COVID-19 was identified at the end of 2019, cytokine storms were known for afflicting some patients who receive bone marrow transplants. These patients develop a complication called graft-versus-host disease, in which the donor marrow mistakes the patient’s own cells for foreign invaders, and attacks them.
In such cases, ruxolitinib has proved successful in interrupting the chain of events that leads graft-versus-host disease to develop into a cytokine storm.
To qualify for the trial involving UW, patients must have tested positive for COVID-19 and must have developed warning signs of an approaching cytokine storm: low oxygen levels and faster breathing.
“We hope that people don’t get to this point in their illness,” said Betsy Nugent, chief clinical research officer for the UW School of Medicine and Public Health, stressing just how severe this phase of COVID-19 is.
Andes said that in a cytokine storm “many (patients) become unconscious as the syndrome progresses.”
There are other treatments used to prevent a cytokine storm in patients suffering from graft-versus-host disease.
Steroids, including dexamethasone, provide broad suppression of the immune system but they can damage organs and raise the risk of patients coming down with secondary bacterial or fungal infections.
“It’s sort of a sledgehammer,” Andes said, stressing that ruxolitinib is more targeted.
At a time when science and medicine are racing to fight the COVID-19 pandemic, UW rushed to qualify as a test site, carrying out preparations that normally take months in just a few weeks.
Andes said that before sites are chosen for clinical trials, doctors, pharmacists and nurses all must be brought up to speed on the study. The work must be approved also by the university’s institutional review board, which monitors all research involving human subjects.