Understanding the United Nations Solidarity Trials
A peek into the global effort against the COVID-19 pandemic.
What is the UN Solidarity trial?
“The Solidarity Trial” is an international clinical trial established to help find an effective treatment for COVID-19, launched by the World Health Organization and it’s partners.
The Solidarity trial will compare four treatment options against the standard of care, to assess their relative effectiveness against COVID-19.
Initially India refrained from participating in the trial. However due to a steep incline in the number of cases, on the 3rd of April 2020, the Medical Council Of India(MCI) agreed to participate, 6 days after the trial formally began in Norway. In India, the trial will be coordinated by Dr. Sheela Godbole, Scientist, at the ICMR National AIDS Research Institute, Pune.
What are the four treatments being investigated?
The four drugs being evaluated are as follows:
- Remdesivir
It is not FDA approved. It is currently being investigated as a treatment option for COVID-19 as an investigative IV antiviral with broad activity that inhibits viral replication through premature termination of RNA transcription and has in-vitro activity against SARS-CoV-2 and in-vitro and in-vivo activity against related betacoronaviruses. It had been earlier tested for the treatment of ebola viruses but failed.
2. Choloroquine & Hydroxycholoroquine
The above mentioned drugs work by decreasing the acidity in endosomes, compartments inside cells that they use to ingest outside material and a point of entry for viruses into cells. But the main entryway for SARS-CoV-2 is a different one, using its so-called spike protein to attach to a receptor on the surface of human cells. Studies in cell cultures have suggested chloroquine have some activity against SARS-CoV-2, but the doses needed are usually high and could cause serious toxicities that can have adverse effects on the patients.
The International community has mixed and obscure reviews about it, “Researchers have tried this drug on virus after virus, and it never works out in humans. The dose needed is just too high,” says Susanne Herold, an expert on pulmonary infections at the University of Giessen, while it has been endorsed by the American and the French Governments for significantly reducing viral load in various patient groups.
3. Kaletra (Ritonavir/Lopinavir)
Lopinavir is specifically used to inhibit the protease of HIV, an important enzyme that cleaves a long protein chain into peptides during the assembly of new viruses. Ritonavir in addition to lopinavir enables it to persist longer.
Although the drug is generally safe, it may interact with other medication also given to severely ill patients, and doctors have warned it could cause significant liver damage.
Lopinavir/Ritonavir did not show promise for treatment of hospitalized COVID-19 patients with pneumonia in a recent clinical trial in China. This trial was underpowered, and lopinavir-ritonavir was then considered for trial again by WHO.
4. Ritonavir/Lopinavir with Interferon beta
The trial will also have an arm that combines the two antivirals with interferon-beta, a molecule involved in regulating inflammation in the body that has also shown an effect in animals tested with MERS. A combination of the three drugs is now being tested in MERS patients in Saudi Arabia in the first randomized controlled trial for that disease, the trial called “MIRACLE” has been underway since 2017 and is funded by the kingdom.
But the use of interferon-beta on patients with severe COVID-19 also possess a certain risk as it can lead to grave tissue damage, if administered improperly.
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