WHO Launches Global Megatrial of the Four Most Promising Coronavirus Treatments

Mar 23, 2020 | Chloroquine, Coronavirus, COVID-19, Global Clinical Trial, Global Health, Hydroxychloroquine, Remdesivir, Ritonavir/lopinavir, SOLIDARITY Trial, World Health Organization

WHO Launches Global Megatrial of the Four Most Promising Coronavirus Treatments

On Friday March 20, 2020, the World Health Organization (WHO) announced a large global trial, called SOLIDARITY, to find out whether any can treat infections with the new coronavirus for the dangerous respiratory disease. It’s an unprecedented effort—an all-out, coordinated push to collect robust scientific data rapidly during a pandemic. The study, which could include many thousands of patients in dozens of countries, has been designed to be as simple as possible so that even hospitals overwhelmed by an onslaught of COVID-19 patients can participate. 

With about 15% of COVID-19 patients suffering from severe disease and hospitals being overwhelmed, treatments are desperately needed. So rather than coming up with compounds from scratch that may take years to develop and test, researchers and public health agencies are looking to repurpose drugs already approved for other diseases and known to be largely safe. They’re also looking at unapproved drugs that have performed well in animal studies with the other two deadly coronaviruses, which cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS).

Study Details and Add-Ons

The design is not double-blind, the gold standard in medical research, so there could be placebo effects from patients knowing they received a candidate drug. But WHO says it had to balance scientific rigor against speed. The idea for SOLIDARITY came up less than 2 weeks ago, says Henao-Restrepo, and the agency hopes to have supporting documentation and data management centers set up next week. “We are doing this in record time,” she says.

On Sunday, INSERM, the French biomedical research agency, announced it will coordinate an add-on trial in Europe, named Discovery, that will follow WHO’s example and will include 3200 patients from at least seven countries, including 800 from France. That trial will test the same drugs, with the exception of chloroquine. Other countries or groups of hospitals could organize add-on studies as well, Heneo-Restrepo says. They are free to do additional measurements or observations, for instance on virology, blood gases, chemistry, and lung imaging. “While well-organized additional research studies of the natural history of the disease or of the effects of the trial treatments could well be valuable, they are not core requirements,” she says.

Treatments that SOLIDARITY will test:

Remdesivir: The new coronavirus is giving this compound a second chance to shine. Originally developed by Gilead to combat Ebola and related viruses, remdesivir shuts down viral replication by inhibiting a key viral enzyme, the RNA-dependent RNA polymerase. TrialSite News recently covered a story of a CA woman whose condition was improved with Remdesivir.  

Chloroquine and hydroxychloroquine: The WHO scientific panel designing SOLIDARITY had originally decided to leave the duo out of the trial, but had a change of heart at a meeting in Geneva on 13 March, because the drugs “received significant attention” in many countries, according to the report of a WHO working group that looked into the drugs’ potential. The widespread interested prompted “the need to examine emerging evidence to inform a decision on its potential role.”

Ritonavir/lopinavir: This combination drug, sold under the brand name Kaletra, was approved in the US in 2000 to treat HIV infections. Abbott Laboratories developed lopinavir specifically to inhibit the protease of HIV, an important enzyme that cleaves a long protein chain into peptides during the assembly of new viruses. Because lopinavir is quickly broken down in the human body by our own proteases, it is given with low levels of ritonavir, another protease inhibitor, that lets lopinavir persist longer. The combination can inhibit the protease of other viruses as well, specifically coronaviruses. It has shown efficacy in marmosets infected with the MERS virus, and has also been tested in SARS and MERS patients, though results from those trials are ambiguous.

Thousands of patients

The design of the SOLIDARITY trial can change at any time. A global data safety monitoring board will look at interim results at regular intervals and decide whether any member of the quartet has a clear effect, or whether one can be dropped because it clearly does not. Several other drugs, including the influenza drug favipiravir, produced by Japan’s Toyama Chemical, may be added to the trial.

To get robust results from the study, several thousands of patients will likely have to be recruited, says Henao-Restrepo. Argentina, Iran, South Africa, and several other non-European countries have already signed up. WHO is also hoping to do a prevention trial to test drugs that might protect health care workers from infection, using the same basic protocol, Henao-Restrepo says.

The trial’s European counterpart, Discovery, will recruit patients from France, Spain, the United Kingdom, Germany, and the Benelux countries, according to an INSERM press release today. The trial will be led Florence Ader, an infectious diseases researcher at the University Hospital Center in Lyon.

Doing rigorous clinical research during an outbreak is always a challenge, Henao-Restrepo says, but it’s the best way to make headway against the virus: “It will be important to get answers quickly, to try to find out what works and what doesn’t work. We think that randomized evidence is the best way to do that.”

Call to Action: For more details on this global study, see the source link. We also invite you to sign up for our Daily Newsletter as we continue to keep readers updated on the COVID-19 pandemic.

7 Comments

  1. Giusy

    Thanks.
    I think that this is the best way to act now.

    Giusy Ranucci, MD, PhD
    Pediatrician

    • TrialSite

      Thanks for the comment Dr. Giusy, Action is surely needed.
      Publisher

  2. Paula Keller

    It is since end of January 2020 that we know Remdesivir and Chloroquine work effectively against SARS-CoV2 in vitro. Over two month and more than 500.000 confirmed cases later it’s still unknown if they work in vivo. We already should have the answers available not starting new trials now. For sure better late than never but given the impact of the crisis someone should have acted much earlier.

    • TrialSite

      Dear Paula,
      There is anecdotal data as to these drugs working on a case by case basis but their is not the systematic evidence of the type required for approval by the medical authorities around the world (e.g. FDA, EMA, etc.). For that is where the randomized controlled trial comes in and that is what is occurring now. At TrialSite News we have seen an intense ramp up of clinical research worldwide and will track and report on a daily basis so we can collectively get to the truth.
      There are deeper and fundamentally more concerning questions that need to be answered. For example, when the virus started was information contained and even censored? There are reports, we will be looking into, that this contagion started earlier than end of December and that certain governments kept it quiet. We cannot be sure but will surely look into it so that if that is the case the people can hopefully hold governments more accountable. Thanks for your comments and being a reader. You matter.

      Publisher

    • ThatPat

      Paula Keller, They have also known since 2005 that Chloroquine kills and prevents SARS-CoV (in vitro) so I wonder why researchers did not suggest it be studied on humans against the SARS-CoV2 sooner. Could have saved many lives.
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1232869/

  3. ThatPat

    MUST SEE…3/2820 Excellent News: Hydroxychloroquine-Zithromycin-Zinc Cocktail Effective on 600 NY Patients – Dr. Vladmir Zelenko shares a preliminary study outlining that out of all his patients treated, he has had ZERO deaths, ZERO intubations, and four hospitalizations.

    https://youtu.be/1TJdjhd_XG8?t=1m24s (40 mins) \
    or if you are short on time, at least watch the last 20 minutes using this link…. https://youtu.be/1TJdjhd_XG8?t=19m20s (20 mins)

  4. Johan Haux

    Dear Friends,
    I think it would be extremly interesting to evaluate cardiac glycosides, especially digitoxin in this setting, see my regent

    communication in BMJ;
    https://www.bmj.com/content/368/bmj.m1252/rr-6
    Sincerely
    Johan Haux, MD, PhD
    Consultant oncologist
    SkaS
    Sweden

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