China has more than 80 clinical trials underway on potential treatments for COVID-19, the disease caused by a coronavirus that has so far killed nearly 1,400 people and infected more than 48,000 across China .
New pharmaceutical drugs are listed alongside traditional millennial therapies in a public registry of clinical trials in China, which is growing daily. There is no known cure, and doctors are keen to help people with the disease, but scientists warn that only carefully done tests will determine which measures work.
Soumya Swaminathan, Chief Scientist of the World Health Organization (WHO), says its teams have taken stock of the many trials in China, as well as the development of a plan for a clinical trial protocol which could be administered simultaneously by doctors. If the Chinese trials, which include up to 600 people each, are not designed with strict standards for study parameters, such as control groups, randomization, and clinical outcome measures, efforts will be in vain. WHO is therefore working with Chinese scientists to establish standards from the start. For example, a person’s recovery or decline stages should be measured in the same way, regardless of the treatment tested. “We hope we can bring some sort of structure to the whole,” says Swaminathan.
The WHO clinical trial protocol is designed to be flexible and allow researchers around the world to pool their results over time. He will compare two or three therapies supported by scientific evidence, including a combination of HIV drugs (lopinavir and ritonavir) and an experimental antiviral called remdesivir.
China has already started trials on the drugs that will be included in the WHO master plan. The Chinese Register of Clinical Trials, a database of biomedical studies in China, lists these surveys among dozens of other controlled trials on existing therapies, experimental procedures and traditional medicines. These treatments have different amounts of evidence that support their effectiveness.
Both anti-HIV drugs block the enzymes that viruses need to replicate. In animal studies, they reduced the levels of coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) 1. Remdesivir, a nucleotide analogue manufactured by biotechnology company Gilead in Foster City , California, has also had some success against coronaviruses in animals2. In January, researchers reported that someone in the United States had survived COVID-19 infection after being treated with remdesivir3. In the first week of February, China launched two placebo-controlled trials of remdesivir, which are expected to include 760 people with COVID-19. The studies are expected to be completed by the end of April and the remdesivir could be approved by the Chinese authorities as early as May, said Shibo Jiang, a virologist at Shanghai Fudan University. “But the epidemic could have disappeared by then,” he said.
China has launched trials to test chloroquine, a malaria drug that has eliminated the new coronavirus (recently called SARS-CoV-2) in cell culture4. And researchers are studying whether steroids reduce inflammation or cause harm to people with severe COVID-19. “It will be interesting to see these results”, explains Yazdan Yazdanpanah, epidemiologist at INSERM, in Paris. Clinical researchers around the world will need this information if the epidemic continues to spread, he added.
Another study, a controlled trial of 300 people, will analyze the serum of COVID-19 survivors. The basic strategy, based on the idea that the antibodies a person constantly builds up to fight a virus can quickly help a newly infected person to fight it, has been modestly successful when used to treat others viruses in recent decades.
Two stem cell trials are also listed in the Chinese registry. In one case, a team from the first affiliated hospital of Zhejiang University will inject 28 stem cells derived from menstrual blood and compare the results with those of people who did not receive the infusions. So far, there is little evidence that stem cells kill coronavirus infections. Swaminathan says WHO can’t control what researchers do, but says the agency published a guide to the ethics of conducting trials in epidemics in 2016. And it will soon publish a brief report and more accessible on the subject.
Fifteen trials included in the Chinese registry plan to enroll more than 2,000 people in total in studies on a variety of traditional Chinese medicines. One of the most important evaluates shuanghuanglian, a Chinese herbal medicine that contains extracts of dried fruit lianqiao (Forsythiae fructus), which has been used to treat infections for more than 2000 years. The trial had 400 participants, including a control group who received standard care but not placebo therapy.
WHO is working with Chinese scientists to standardize the design of all studies, including those of traditional medicines. The efforts come from a controversial movement last year, in which the organization recognized traditional Chinese medicine in its collection of diseases. Critics have argued that recognizing WHO equals support, but Swaminathan disagrees. She says the WHO measure helps the organization to code medical terminology so that herbal remedies can be assessed with the same rigor expected from pharmaceutical tests. “We want a scientific approach to try traditional medicine,” she says.
As these trials take off, researchers are looking for new drugs that fight multiple coronaviruses, including those that have not yet appeared. A peak protein on the surface of the viruses underlying SARS, MERS and COVID-19 provides a tempting goal. Already, Jiang and other research groups have found compounds and antibodies that project onto this pic6, which could prevent coronaviruses from invading human cells.
With many therapeutic options and a limited time, the WHO should provide advice on which treatments to advance and which to discontinue as trials progress.