- The WHO will restart its Solidarity trial after the first one tested four drugs that didn't show promising results
- The trial has recruited more than 11 000 participants across 30 countries
- In the new trial, researchers will test three existing drugs' effect on hospitalised Covid patients
A new international clinical trial that will test potential Covid-19 therapies is about to start, according to a report by Nature.
The clinical trial, named Solidarity, is coordinated by the World Health Organization (WHO), who will look at three drugs in particular and their ability to decrease inflammation in Covid patients – an approach, the report notes, that has already shown promise in people hospitalised with the disease.
The WHO launched Solidarity in March 2020, but the study centred on antiviral drugs at the time. The trial had enrolled more than 11 000 participants hospitalised with Covid in 30 countries by October 2020, but the leaders of the study found that none of the four drugs tested reduced hospital stay or prevented death.
The four drugs tested at the time were remdesivir, interferon, hydroxychloroquine (the malaria drug), and a combination of HIV drugs (lopinavir and ritonavir).
“The Solidarity Trial published interim results on 15 October 2020. It found that all four treatments evaluated ... had little or no effect on overall mortality, initiation of ventilation and duration of hospital stay in hospitalised patients,” researchers said, adding: “The Solidarity Trial is considering evaluating other treatments to continue the search for effective Covid-19 therapeutics.
'Promising signals' needed
John-Arne Røttingen, scientific director of the Norwegian Institute of Public Health and chair of the Solidarity trial's international steering committee reiterated this in the Nature article, saying: “None of the antivirals has shown strong effects in hospitalised patients. The emerging consensus is that it’s too late. Where the antiviral medications could have a benefit is quickly after a positive test.”
The three drugs were carefully selected based on the promise they showed in smaller clinical trials and widespread availability, explained Røttingen.
The drugs are infliximab, imatinib, and artesunate.
“You need at least promising signals that some of them will work,” said Røttingen. “And we need to study drugs that we can deliver in a broad group of countries.”
In the trial testing the three drugs, the team hopes to focus instead on reining in immune responses that can contribute to severe forms of Covid.
A closer look at the three drugs
Infliximab (also known as remicade in the US and revellex in SA) is a drug used to treat autoimmune conditions such as Crohn’s disease, rheumatoid arthritis, and psoriasis.
According to the Nature article, this drug blocks a protein known as tumour necrosis factor alpha, which is released by immune cells called macrophages and is responsible for promoting inflammation.
The second drug, imatinib, is a cancer drug that researchers hope will target both the SARS-CoV-2 virus (which causes Covid disease) and inflammation by blocking the virus from entering human cells, and ultimately reduce the activity of pro-inflammatory proteins called cytokines. These proteins regulate our immune system and how our body reacts to internal and external stress, including cancer and inflammation.
However, some Covid patients experience "cytokine storms’" where there is an overproduction of various inflammatory cytokines, explains News-Medical. The condition is life-threatening and has been described as one of the main causes of death in a certain sub-group of patients, Health24 previously reported.
Artesunate, the third drug to be tested, is an anti-malaria drug with potential anti-inflammatory properties. The drug was registered in South Africa in 2017 as a malaria treatment.
Røttingen explained that each of these drugs will be given alongside standard care. In many regions across the world, this includes dexamethasone.
Dexamethasone beneficial, but room for improvement
Dexamethasone, a corticosteroid, which is also used in a wide range of conditions for its anti-inflammatory and immunosuppressive effects, was labelled as a breakthrough Covid treatment in June 2020 after a large trial showed promising results, noted this Health24 article.
According to the results, the steroid was shown to reduce mortality by about a third, and for patients requiring only oxygen, mortality was cut by about a fifth.
Since then, it has become the standard care in several countries for hospitalised Covid patients who need breathing assistance, Anthony Gordon, an anaesthesiologist at Imperial College London told Nature, while adding that there is still room for improvement: “We know that some patients remain sick even with those treatments,” he said.
Therefore, with the second WHO trial, the researchers are hoping that these three drugs will work to shut off particular immune responses.
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