Paris (AFP)

A major clinical trial has just been launched for four experimental treatments against the coronavirus in several European countries. With what hope? Overview of this large-scale test against Covid-19 disease, for which there is currently no treatment.

Methodology

The Discovery trial, launched Sunday, is to include 3,200 European patients in France, Belgium, the Netherlands, Luxembourg, the United Kingdom, Germany and Spain - and possibly other countries.

Each patient included is allocated one of the four therapeutic treatments tested randomly, after computer randomization - it is not the doctor who chooses. "This allows the trial to be sampled," explained Professor Florence Ader, an infectious disease specialist at the Croix-Rousse hospital at the Lyon University Hospital, who is piloting the project, during a press briefing.

The patients concerned

In France (800 participants), only hospitalized patients in the infectious disease and intensive care departments are eligible for the trial.

These are patients with respiratory signs, especially pneumonia, and / or needing an oxygen support, details Pr Ader.

The treatment was administered to them quickly, "because the delay in starting treatment seems to be an important factor in this disease," according to the infectious disease specialist. Indeed, the more we advance in the disease, the less the presence of the virus is important, so "if we want to hope for an anti-viral effect of a molecule, it must be given very early", says Professor Bruno Lina virology at the Lyon University Hospital.

The molecules tested

They must always combine two skills: efficiency and tolerance.

- Remdesivir:

It is an antiviral initially designed for the Ebola virus but "which has a wider spectrum of action", because it "interacts with other viruses, and it is notably capable of blocking the replication of this new coronavirus", details Bruno Lina.

"We hope a lot in this molecule" because "the first results in vitro were very good", comments the virologist.

- Lopinavir in combination with ritonavir:

This is the "recycling" of a drug against HIV, which "consists in blocking the replication of the virus", according to the researcher: "we realized that it works in the test tube".

This combination has already been tested in China, but with mixed results, especially because many patients "were included very late, sometimes beyond the 10th day of the disease," said Professor Lina. The Discovery test, launched much earlier in the evolution of the Covid-19, will therefore be "complementary" to the Chinese test.

- The same combination lopinavir / ritonavir, associated with interferon beta:

This association is considered interesting since Covid-19 disease comprises two phases: a virological phase, "for which it is believed that anti-virals can have a significant effect", and a phase with "an inflammatory syndrome which can lead to degradations. in the lungs, and we hope that interferon can block this inflammatory process, "said the virologist.

- Hydroxychloroquine:

This fourth treatment, a cousin of chloroquine, an anti-malaria drug which is causing much debate, was not planned at the start. It has been added at the request of the WHO and the French State.

"It seemed logical to us" to add it because "recent data were provided to us, in particular a Chinese paper published on March 9 in the largest American infectious disease journal, which brought a number of interesting arguments ", underlined Florence Ader.

Why hydroxychloroquine rather than chloroquine? Both molecules work the same way, but hydroxychloroquine poses less risk of toxicity.

Delays

In France, the first treatments started on Sunday at the Bichat hospital in Paris and at the Lyon University Hospital. The selection of hospitals is "based on the mapping of the epidemic", and the recruitment of 800 French patients will be completed "as soon as possible".

In the other countries, "it will be based on the ability of the countries to start their respective trials," says Professor Ader.

The first clinical evaluation will take place on the 15th day of treatment, "so in the coming weeks, we will begin to have the first results", she predicts.

If successful

As soon as a trial "has shown the superiority of one of the four treatment regimens, we will be able to suggest to regulators, in France and worldwide, to use it", say the experts.

The treatment can then be released "very quickly", given that "we are in a situation of therapeutic deficiency", they emphasize, calling however for "caution" because "we do not yet know their effects".

© 2020 AFP