Solidarity confirms the ineffectiveness of several anti-covid treatments

Launched on March 18 by the WHO, the Solidarity clinical trial was slow to deliver its results. Expected in July, they have just been published on the medRxiv prepublication server. The objective of this international randomized study, the largest in the world with more than 12,000 participants in more than 400 hospitals across 30 countries, was to assess the effectiveness against Covid-19 of already existing treatments.

Alas, none of them have proven themselves. “The interim results of the Solidarity therapeutic trial indicate that treatments with remdesivir, hydroxychloroquine, lopinavir / ritonavir and interferon appear to have little or no effect on 28-day mortality or on outcome. of Covid-19 in hospitalized patients, ”summarizes the WHO on its website. Other uses of these molecules, in prevention or in people suffering from milder forms of the disease, were not evaluated in this trial.

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Solidarity’s results confirm those of other smaller trials, including the European Discovery and the British Recoveryl, which had already concluded that certain drugs, including hydroxychloroquine, were ineffective in hospitalized patients. Only remdesivir, an antiviral initially developed against Ebola, remained in the race. Previous studies suggested that it slightly shortens the recovery time of patients, but Solidarity shows that it does not make a difference in terms of mortality.

A large-scale study

Why is the publication of these results only now, when many of its conclusions are already known and some segments of the trial were dropped as early as the summer? “We could have published only the results on the ineffectiveness of certain treatments, but that would have been a partial publication. The idea of ​​Solidarity is to have a single study for all of this first group of treatments, ”explains Oriol Manuel, assistant doctor in the infectious diseases department of the CHUV, responsible for coordinating the study in Switzerland.

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If the international character of Solidarity is an asset for the quality of its results, it has also complicated its implementation. Not all countries are in the same position when it comes to submitting their data to WHO. “In Switzerland, we have a dedicated team to include patients, but in other countries it is clinicians who are overwhelmed by the treatment of patients,” emphasizes Oriol Manuel. Which means having a complete database takes time. ”

Recruitment sometimes complicated

The Swiss section is a good illustration of the difficulties inherent in the protocol. Out of a target of 500 patients, only about sixty were able to take part in the trial. Which is not necessarily surprising, according to Manuel Oriol: “We joined the trial at the time of the peak of the epidemic. The authorizations to set up the study were issued in three weeks, which is fast, but the integration of patients began when the epidemic had already subsided. ” The biggest contributors in terms of patients are mainly located in South America, where the virus continues to circulate.

In France, the Discovery trial, adapted from that of the WHO, encountered other types of problems. Several French doctors indicated that patients refused to be included in the trial since they had only one chance in five of being treated with hydroxycholoroquine (including the control arm). The excitement around this molecule widely publicized by the microbiologist Didier Raoult of the Marseille University Hospital Institute has also hampered the progress of clinical trials in other countries, as evidenced by an article published in Nature last April, but this did not happen in Switzerland.

An identified treatment

While large-scale clinical trials have all encountered operational difficulties, one has already published results: the British Recovery study. In particular, it has made it possible to identify an effective treatment in patients placed on respiratory assistance, dexamethasone.

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This treatment was not taken into account in the other trials because it belongs to the corticosteroid family, initially contraindicated in the treatment of Covid-19. “In March, dexamethasone was considered to pose a risk of increasing viral load. When Recovery chose to integrate it, it was daring, says Oriol Manuel. Solidarity focused on treatments with an antiviral effect, not anti-inflammatory or immunomodulatory treatments. ”

This new family could therefore be integrated into Solidarity, which was designed as an evolving trial, and for which patient recruitment continues. The WHO thus indicates that new antivirals, immunomodulators and monoclonal antibodies could be the subject of an evaluation.