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The World Health Organization said Wednesday that it would launch a multiarm, multicountry clinical trial for potential coronavirus therapies, part of an aggressive effort to jumpstart the global search for drugs to treat Covid-19.

Four drugs or drug combinations already licensed and used for other illnesses will be tested, said WHO Director-General Tedros Adhanom Ghebreyesus. Ten countries have already indicated they will take part in the trial.

The mere fact the WHO is sponsoring the trial suggests that efforts in China to test these drugs may not have come up with enough data to indicate whether any were of use to prevent patients from developing severe disease or save those with severe disease from death.

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The study, which Tedros said he hopes other countries will join, has been named the SOLIDARITY trial. Countries that have already signed on are: Argentina, Bahrain, Canada, France, Iran, Norway, South Africa, Spain, Switzerland, and Thailand.

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“Multiple small trials with different methodologies may not give us the clear strong evidence we need about which treatments help to save lives,” he said during a briefing in Geneva.

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Ana Maria Henao-Restrepo, unit head for the WHO’s research and development “blueprint” group, said the trial design was deliberately kept simple “to enable even hospitals that have been overloaded to participate.”

“This trial focuses on the key priority questions for the public. Do any of these drugs reduce mortality? Do any of these drugs reduce the time a patient is in hospital and whether or not the patients receiving any of the drugs needed ventilation or intensive care units,” Henao-Restrepo said.

The four drugs or combinations will be compared to what is called standard of care — the regular support hospitals treating these patients use now, such as supplementary oxygen when needed.

The drugs to be tested are the antiviral drug remdesivir; a combination of two HIV drugs, lopinavir and ritonavir; lopinavir and ritonavir plus interferon beta; and the antimalarial drug chloroquine. All show some evidence of effectiveness against the SARS-CoV 2 virus, which causes Covid-19, either in vitro and/or animal studies.

Remdesivir is made by Gilead. Lopinavir and ritonavir are combined and sold as Kaletra or Aluvia by AbbVie.

Later in the day, after close of business in Geneva, the New England Journal of Medicine published a study from China that reported finding that the lopinavir-ritonavir combination did not improve survival or speed recovery, though the authors noted that the very high death rates among patients who received the drugs and those who received only standard care suggest they had enrolled “a severely ill population.”

Of the 199 patients in the trial, 22% died, which was “substantially higher than the 11% to 14.5% mortality reported in initial descriptive studies of hospitalized patients with Covid-19,” they said. The trial was also not blinded — meaning the doctors knew which patients were receiving the drugs — which they acknowledge could have influenced their clinical decision making.

“These early data should inform future studies to assess this and other medication in the treatment of infection with SARS-CoV-2,” wrote the authors. “Whether combining lopinavir–ritonavir with other antiviral agents, as has been done in SARS and is being studied in MERS-CoV, might enhance antiviral effects and improve clinical outcomes remains to be determined.”

Henao-Restrepo said chloroquine — which is cheap and used regularly around the world — will be tested two ways. Some countries will test chloroquine against the standard of care while others will test hydroxychloroquine, a related drug.

“The good thing about the trial is … that the randomization could be adjusted to the drugs available in each individual hospital over time,” Henao-Restrepo said. “The other good thing … is that we can include additional arms or drop arms as our global data safety and monitoring committee advises we should do.”

Enrolling patients across a number of countries should speed the world to an answer about which drugs, if any could be effective in reducing the toll of Covid-19. The WHO launched a similar trial in the Democratic Republic of the Congo in November 2018 to test four therapies against Ebola.

At the time of that launch, it was thought that the trial might need to draw data from several Ebola outbreaks before it could reach an answer. But the North Kivu outbreak, which could be declared over next month, was so large results were announced in August 2019. Given the high number of cases globally of Covid-19 and the number of countries participating, results should come faster with this trial.

This story had been corrected to remove an error about where hydroxychloroquine can be used. It has also been updated.

  • Pneumonia or drugs related to respiratory system should also be tested in laboratory with some higher dosage in grams so it may be effective.

  • Finally some proper talk about the cure which is great to know. Up until now the world was shocked and scrambling for prevention but slowly we are realizing prevention would be almost impossible, at least for now. UN needs to call an emergency digital General Assembly session where all countries develop consensus and declare war against Corona Virus no matter what their differences are. A global policy and guideline should be created to fight this virus and to bring some stability and order to calm the citizens across the globe. The likes of IMF and WB have a crucial few months ahead of them and need to ensure global economic stability which trickles down to the common man who is at the bottom of the pyramid. At the same time global news agencies and social media networks need to band together to fight and eliminate the menace of misinformation, rumors and create policies that provide factual information but don’t cause panic. Social media networks and digital agencies should create technology that helps people in connecting online while adopting social distancing. Top mental health organizations should provide guidelines and create digital content, series and shows that help calm citizens of the world and how they could cope with the mental stress this virus is causing. Leadership from all religions should give a message of social distancing as part of which they discourage mass religious, cultural and national congregations and give a message of hope, unity and optimism. Finally, we the general public need to realize that this virus is causing great damage right now and it can cause much more damage if we don’t realize our responsibility of social distancing. We also need to empathize and help those in need of help in whatever way we can and lastly stop panicking and accepting our current reality with a sense of cautiousness and hope. May the human race overcome this challenge soon.

  • Terrific article, especially the discussion of the lopinavir-ritonavir research.

  • Is anyone in the Biomed community developing an anti-coronavirus drug based on restrictive enzymes? That would at least stop the spread of the virus in the body. In the bacterial cell, restriction enzymes cleave foreign DNA, thus eliminating infecting organisms.

  • I heard about chloroquine works and cheap (from China Dr.). But, do not expect 100% cure rate.

  • studies on SARS show tissue tropism for the apical surface of mucus membrane, esp ciliated epithelium. Also quinine has been shown to be antinflammatoy teatment for asthma when inhaled. Someone should try aerosolized chloroquine. Membrane surface cells are notoriously difficult to treat with systemic drugs.

  • I would like yo participaste in the study. I’m physician from Guatemala. Thank you!

  • Lars Ostberg, PhD
    Elisabeth Harfeldt
    Alice Alonso, PhD
    Made monoclonal antibodies for viruses. Great talent!! Please use them.
    Thank you.
    God bless everyone.
    Hema Parekh

  • Hopefully this laudable collaborative effort is productive. It would however be wise to add a small number of drugs already in phase 2b or 3 clinical trials for closely related viral diseases. Such as : from Mesoblast (MESO), in phase 3 with promising results: remestemcel-L / RYONCIL (for accute respiratory distress syndrome ARDS). And from Vaxart (VXRT) in phase 2b : vapendavir (ORAL drug for human rhinovirus HRV upper respiratory infections) as also BTA074 (oral infusion in phase 2 for respiratory syncytial virus RSV). It could very well be these new drugs that specifically target viral lung infections that are the key to attack the virility of this globally fast-spreading potent virus. Any patient in advanced distress would no doubt be willing to participate in fast-tracked trials for these developing drugs.

    • What is the WHO advising Italy to do? Would it be an unreasonable assumption to suggest China has significantly reduced mortality rates, using distribution and testing of these biological treatments? Yet, mortality rates are climbing continuously in Italy and nearly surpass China’s. Can’t the WHO advise Italy on immediate interventions, or at least let the family members decide on acceptance of risk, with perhaps much beneficial results in accepting non-trialled
      drugs ?

    • I agree with the statement regards severely ill patients accepting drugs, that appear to have elements of capability to fight this disease. I doubt however that a consistent message is being provided about potential benefits. Family members should be told of the potential risks vs benefits of using un-trialled drugs.
      I’m sure given the sudden control rates the Chinese have achieved against corona, were achieved by collaboration between front – line health workers, patients and their families. I wonder if this is happening in places like Italy?

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