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.
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.
“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.
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.
Sorry – BUT I think the Lopinavir/ritonavir trial data deserves a second look and should in the current situation be also analyzed from a ‘resource sparring’ effect point of view – as ANY COVID patient who will not need a ventilator or ICU setting in the current situation will be a help. In this regard if one looks at the raw data reported in the NEJM paper:
1. People where enrolled quite late (after being symptomatic for 13 days already….) and it is a very small study (only 200 patients)
2. Please all look at table 2 – section ‘Treatments during study period’ – in the treated group there is in my opinion a definitive numerical trend that the treated patients required LESS intensive therapy (Less vasopressors 17.2 % versus 27 %, less dialysis 3 % versus 6 %, less noninvasive mechanical ventilation 10% versus 19% and less invasive mechanical ventilation 14% versus 18%).
3. Please also look at table 3:
a. Day 28 mortality – early treatment 19% versus 27% (I know the CI cross over but there is definitively a trend there….)
b. BUT PERHAPS MORE IMPORTANT:
ICU length of stay – 6 days versus 11 days (CI ends at 0)
Seven-category scale at day 14 – 2 – not hospitalized 43% versus 28%
– 3 – hospitalization not requiring oxygen 8% versus 24%
4. The drug is a known drug and there was not safety issue seen in the study.
My personal take on this is that if you look at the raw data of the trial (and although the primary endpoint failed – which happens in clinical trial) there are definitively encouraging trends – and using the medications appears to have a ‘resource’ sparring effect which might very much help in the current situation.
Informative article, thank you
My question is;
Any idea how long the clinical trial will take?
Info on chloroquine suggest significant improvement with 3 days, trial began Thursday.
Cuba likes to brag and Administration officials like to belittle Cuba. Any less biased material on the effect of Interferon Alpha 2B, in treating COVID-19?
Sunlight has some effect at fighting COVID-19, but closing Florida’s beaches is not likely to increase the social distancing of the young people who were kicked off the beach, why not keeping the beach open with a threat to close them again if the space between the average beach-goer doesn’t increase?
Drastic measures put off the epidemic a few days, but why is it assumed it will flatten the curve? the-standard.org/news/coronavirus-seriously-sinister-sickness-or-simply-silly-sensationalism/article_d48e9c92-4555-11ea-8221-a3e41efa2b25.html
Silly panic coronvirus
Maybe in some desperate place maybe everyone in a facility might treat the very sick while still recovering from a mild case themselves
The brash beach bums ostentatiously breaking social distance rules hopefully got some firmly corrected for their brain-dead juvenile irresponsible anti-social behavior. Methinks a call from Washington DC to the Florida Governor delivered the immediate results. I hope the community around these purps takes care of more permanent behavioral improvement.
Outstanding and thank you!
The trade name of this drug Avigan has been making the rounds in NHK News (Japan) and CHGTV (China) for at least a week.
The next logical step would be for some aggressive and assertive reporter to aks Tony Fauci at the next Trump Team’s news conference whether he has heard about it and what would be his view. If Tony does not know anything, or refuses to provide an opinion, then he should resign right then. Next another reporter should ask Stepheb Hanh the same question, if he knows nothing or refuses to comment, the he should resign as well. Then a third question by the reporter to Trump would be something like:
“Mr. Predident, since this is drug was developed by Fujifilm Toyama Chemical, would you be eilling to mention and inquire about it when you tlak to Japan’s Prime Minister Abe and as a follow up, would he be willing to import a large quantity of Avigan to the US with NO TARIFF! We can surmise what our POTUS would say right?
Then Trump could give Tony and Stephen the last opportunity to save their jobs and to redeem themselves by asking them “If my friend Abe says he would be happy to let us do that, you two experts won’t have any problems or issues for US to import them in large quantity despite the fact that it has not been approved in the US specifically for Corvid19 treatment, do you?” IMO the politically correct and also the loyal answer should be “Of course not Mr. President!”
Could it be a good idea to also include the drug
Favipiravir, used in Japan and china, to treat this disease?
Correction: NO MORE than two days. Sorry, didn’t catch that before I hit Submit.
Can someone delete this? This comment page is very confusing and I was trying to correct a different comment of mine!
What is the “standard of care” against which chloroquine can be tested. The only care of which I am aware is supportive……
The problem with WHO is that it is to similar to “FIFA”. It needs a bit of “sunshine” in its dark corners.
They have failed to ask for important patient data, current medications since they started to collect patient information. This would be very useful data to mine for good/bad effects for patients already on certain drugs.
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