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WHO launches the SOLIDARITY study, a global mega trial on the 4 most promising coronavirus treatments

The World Health Organization (WHO) has announced a large global trial, SOLIDARITY, to establish the safety and effectiveness of different antiviral drugs in treating COVID-19. The study team plans to recruit thousands of patients from several countries with the aim of collecting data expeditiously; using a simplified process to enable hospital overwhelmed by COVID-19 to participate.

Bernard Kimwei, CRC
Burnaby Hospital, BC

According to the initial data released from Chinese researchers, about 15% of COVID-19 developed severe symptoms requiring hospitalization and oxygen ventilators to help them breathe.  The hospitals in hotspot areas are overwhelmed and the world economy is on the edge of collapse, thus there is a sense of urgency to find a drug or a combination of drugs that can treat or protect people from contracting the virus. Instead of coming up with a new drug combinations to treat COVID-19 treatment, the WHO is collaborating with public health agencies to look into drugs which have already been clinically tested on coronavirus disease, that is, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), as well as  drugs approved to treat HIV and malaria.

Recruitment and Enrolment into SOLIDARITY Study

World Health Organization has instituted a simple recruitment and enrolment process as follows;

  • Patients already confirmed by doctors to have contracted COVID-19 and deemed eligible
  • Doctor completes patient’s data into the WHO website, including any underlying condition that is likely to affect the course of the disease.
  • Patients sign a consent form that is scanned and sent electronically to WHO, and
  • Lastly, patient will be randomized into one of the drugs available at the hospital.

In Europe, a French biomedical research agency, INSERM, will collaborate and conduct a similar trial, Discovery. This will aim to recruit over 3000 participants from over half a dozen European countries, with 25 % from France. The study is set to test same drugs as SOLIDARITY except chloroquine, which is used to treat malaria

Full list of treatments that SOLIDARITY will test is as follows:

REMDESIVIR

Remdesivir was first designed to treat patients with viruses that causes Ebola. However, it was found to be ineffective compared with other drugs in the market. It works by disrupting viral ability to replicate in the body.  Even though the initial studies on Ebola were not a success, a research report from university of North Carolina showed the drug can inhibit the coronaviruses that causes SARS and MERS from duplicating.

Recently, remdesivir has been used in the USA to treat COVID-19 patients, some individuals’ results were encouraging, for example;

  • According to a report published in The New England Journal of Medicine, remdesivir was administered to a young man whose condition had worsened, and improved the next day, and
  • In California, a patient who had a critical condition was administered with remdesivir, later recovered well.

CHLOROQUINE AND HYDROXYCHLOROQUINE

The two drugs have received a wide attention despite their lack of scientific evidence to support their safety and effectiveness in treating COVID-19. The WHO initially planned to omit this combination in its trials, but because the public attention that ranged from prominent politicians, it decided to include to examine, through controlled trials, safety and effective to treat COVI-19 patients.

Some Clinical Studies have indicated chloroquine to have some activity against SARS-CoV-2, a coronavirus family, but researchers have cautioned that high doses are needed and which may lead to high levels of toxins causing harm to patients. Additionally, previous studies using chloroquine against other viral diseases, dengue and chikungunya, and on nonhuman primates infected with the chikungunya were not conclusive.

Chinese researchers reported treating 100 patients with chloroquine and hailed the results in their publication, but the WHO has not been able to access data. Separately, France reported a study where 20 COVID-19 patients were treated with hydroxychloroquine, with encouraging, results but was not randomized and did not report clinical outcomes. Due to the known side effects associated with hydroxychloroquine, treating COVID-19 patients might do more harm than good as most of the patients have underlying health issues that might be aggravated during treatment.

Ritonavir/Lopinavir

The combination of ritonavir and lopinavir was approved in the USA to treat HIV infections. It was developed by Abbott Laboratories, and they belong to a class of protease inhibitors. Lopinavir works by inhibiting the protease of HIV, a crucial enzyme during the formation of new viruses. Recent trials on MERS and SARS have indicated that using ritonavir/ lopinavir can inhibit the protease, however, the final results were inconclusive.

Initial test results on COVID-19 from Wuhan, China, for patients treated with ritonavir/lopinavir was not encouraging either. In the trial, about 200 patients were recruited, one group was administered with a combination of lopinavir/ ritonavir plus standard care or standard care alone. The result was inconclusive since there was no significance between the two groups. In conclusion, the authors sounded optimistic drug combination, stating some of the patients started treatments when they were very ill. This means it may have started too late to have a therapeutic effect.

Ritonavir/Lopinavir and interferon-beta

In the final combination, SOLIDARITY will run a study comprising of ritonavir/lopinavir with interferon-beta, a molecule that blocks the action of gamma interferon and helps in regulating inflammation in the body and it has shown effect in treating patients with MERS. But researchers need to be cautious as use of interferon-beta on COVID-19 may cause serious tissue damage if administered in late stage of disease.

Global Recruitment

SOLIDARITY study is aiming to recruit thousands of patients. So far, several non-European countries have signed up to this program. For the European countries, all the trials will be managed by Discovery, and it will recruit patients in France, Spain, the UK, German and the Benelux countries.

Reference:

Kai, C, (2020, March 22). SOLIDARITY. WHO launches global megatrial of the four most promising coronavirus treatments. Retrieved from

https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments#