World Health Organisation launches large trial into COVID-19 treatments
The World Health Organisation (WHO) has launched a huge trial, called SOLIDARITY, to assess the efficacy of four different treatments against SARS-CoV-2 (the Coronavirus) and COVID-19.
The four treatments that the WHO will be studying are:
- Remdesivir (an experimental antiviral)
- Chloroquine and hydroxychloroquine (an anti-malarial combination)
- Lopinavir and ritonavir (HIV antiretrovirals)
- Lopinavir, ritonavir, and interferon-beta
In recent days the US President, Donald Trump, noted his administration's interest in studying chloroquine and hydroxychloroquine further, and whilst study into the HIV combination in China failed the WHO believe it's worth investigating in a larger trial.
The WHO has worked to make enrolment of COVID-19 patients easy with doctors in dozens of countries able to enter the patient details and underlying health conditions via a web portal. The portal will then randomise a treatment for the patient based on what's available at that hospital - or within the local treatment protocols.
There is no onerous data entry or additional paperwork required. Doctors will only be asked to enter the patient outcome (recovery/death), duration of hospital stay and what level of respiratory support they needed.
"It will be important to get answers quickly, to try to find out what works and what doesn’t work. We think that randomised evidence is the best way to do that", said Ana Maria Henao Restrepo of the World Health Organization.
The list of treatments the WHO will be studying was put together by a panel who've been monitoring ongoing treatment efforts since the beginning of the outbreak and chose four courses of treatment that showed promise, safety, and availability. The design of the trial is designed to be flexible, with the panel able to add in more treatment protocols as they show promise.
Remdesivir
This compound was developed by Gilead Sciences to combat Ebola and related viruses, remdesivir shuts down viral replication by inhibiting a key viral enzyme, the RNA-dependent RNA polymerase. Early indications are that it's most effective when given early on in the infection. Treatment is by an IV line, which means it's only suited for in-patient settings.
Chloroquine and hydroxychloroquine
These decades old drugs are commonly used to treat malaria, but thanks to the pandemic are seeing a resurgence in popularity - aided in part by President Trump's premature endorsement of the combination on Friday (20 Mar). There are concerns about the toxicity of this combination given the high doses required.
Ritonavir/lopinavir (Kaletra)
Whilst these HIV antiretrovirals have largely fallen out of favour in the developed world since their approval in 2000, they've been in the spotlight as a possible treatment for SARS-CoV-2 and COVID-19. These protease inhibitors halt an important process, known as protease, in the viral replication cycle. Initial Chinese trials (199 patients) have not shown efficacy, but the WHO believes it merits a closer look.
Lopinavir, ritonavir, and interferon-beta
The fourth arm of SOLIDARITY combines both the two HIV antiretrovirals outlined above, but also interferon-beta - a treatment that helps regulate our body's inflammation. This course is not without its risks, timing is critical to prevent the treatment itself doing more harm than good.
SOLIDARITY has already recruited patients from Argentina, Iran, South Africa, and several other non-European countries.
Discovery, SOLIDARITY's European counterpart, will recruit from Germany, Spain, France, Belgium, Netherlands, and Luxembourg. Discovery will be co-ordinated by the French biomedical research agency INSERM and led by Florence Ader, an infectious diseases researcher of the University Hospital Center in Lyon, France.