Antiviral drugs that had held promise as a potential treatment for the coronavirus did not work in one of the first major studies in seriously ill patients, researchers from China reported Wednesday.
“No benefit was observed,” the researchers wrote in The New England Journal of Medicine.
The study tested Kaletra, a combination of two antiviral medicines, lopinavir and ritonavir, that are normally used to treat HIV.
There is no proven drug treatment for the new coronavirus, and doctors around the world have been desperately testing an array of medicines in hopes of finding something that will help patients, especially those who are severely ill. Several antiviral drugs have been considered possible treatments, though so far none has proved effective.
Even though the results were disappointing, the researchers said that this one study was not the last word, and suggested that more studies might determine whether the drugs would work if given earlier in the illness or in combination with other medicines.
The new findings involve a study of 199 adults, ages 48 to 68, who were hospitalized and severely ill with the virus at Jin Yin-Tan Hospital in Wuhan, China.
For 14 days, half of the patients received standard care alone, and half were given the antiviral drugs plus standard care. Standard care includes the usual treatments for pneumonia, including oxygen if needed, and other medicines needed to keep patients stable and comfortable. The drugs did not shorten the illness or prevent deaths.
An editorial published along with the article called the research “a heroic effort,” saying it was proof that useful studies could be done, even in the midst of an overwhelming pandemic.
Earlier reports from China showed that doctors were pulling out all of the stops to try to help their patients, dosing them with antibiotics and antiviral drugs to try to fight off the virus and bacterial infections that they feared might complicate the illness. Some patients were also given steroids or other drugs in an effort to tamp down severe inflammation, an overreaction by the immune system that could be fatal.
There is no solid evidence yet that anything works, but the epidemic is moving so fast that doctors are trying approaches where even preliminary data suggests there may be a benefit. Many feel they are on their own to develop treatment protocols. Federal health authorities like the Centers for Disease Control and Prevention recommend supportive care, but have said there is no evidence yet to support antiviral drugs or treatments for inflammation.
“If I’m out in the community and I’ve got somebody who’s dying, of course I would do whatever I could to try and help them,” said Dr. Tim Schacker, the vice dean for research and an infectious disease specialist at the University of Minnesota medical school.
A number of hospitals were giving coronavirus patients hydroxychloroquine, an old, inexpensive and relatively safe malaria drug that lab studies indicated might keep the coronavirus from invading human cells. Reports of its use in patients in China and in France have suggested that it may help, but there is not enough data to be sure.
Nonetheless, the idea is catching on, so much so that shortages of the drug are being reported.
In Seattle, many hospitals have signed up to enroll patients in a clinical trial of Gilead’s experimental antiviral drug remdesivir. The trial is a controlled study, meaning that some patients will be picked at random to receive placebos rather than the drug — the gold-standard type of study to determine whether a drug really works.
Dr. James Town, director of the medical intensive care unit at Harborview Medical Center in Seattle, said that the first choice for most patients would be the remdesivir study. Those not eligible for the study could apply to the Food and Drug Administration for “compassionate use,” special permission sometimes given to receive an experimental drug outside of a study.
After remdesivir, Town said, the next choice would be hydroxychloroquine, as long as the patient did not have abnormalities in heart rhythm, which would make the drug unsafe.
For critically ill patients suffering from intense inflammatory reactions, called a cytokine storm, some centers are trying a drug called tocilizumab.
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“That’s the creative juice we need right now, as we try and take care of these patients literally on the run,” Schacker, from the University of Minnesota, said.
Town said: “There are trials going on for some of these things in some areas. All are rapidly enrolling, but their data won’t be back in time for a lot of places to make these decisions.”
The University of Minnesota is conducting three studies, including one on remdesivir for seriously ill patients. A second study will give hydroxychloroquine to people who have been exposed to the coronavirus, because they live in the same household as patients, to see if the drug can prevent them from becoming infected.
The third study will use an old, safe drug called losartan, normally given to treat high blood pressure, to find out whether it can prevent mild coronavirus infections from turning more serious. The drug blocks the receptor that the virus uses to get into cells, so researchers think it might stop or slow the illness.
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“We’re trying to ask the question in the midst of the confusion and everything that’s going on, ‘Do these drugs help? Yes or no?’” Schacker said. “If no, let’s move on.”