ACTT-2 trial to test remdesivir with another drug against COVID19

Remdesivir along with a powerful anti-inflammatory agent could be the key to treating the most severe COVID-19 cases

After the early promising results from the first stage of the Adaptive Covid-19 Treatment Trial (ACTT-1) in the treatment of critical COVID-19 patients, researchers have now begun the next stage of the trial by combining Remdesivir along with a powerful anti-inflammatory agent, baricitinib. The trial is called ACTT-2.

Remdesivir, developed by Gilead Sciences Inc., is a broad-spectrum antiviral originally meant to be used in the treatment of Ebola virus disease. It has shown promise as a drug against the  Middle East Respiratory Syndrome (MERS) and severe acute respiratory syndrome (SARS), both of which, like COVID are caused by coronaviruses. It is also a part of the SOLIDARITY trial of WHO under which it is likely to be used also in Indian patients.

Baricitinib, developed by Eli Lilly and Company, is used for reducing inflammation associated with rheumatoid arthritis. Researchers want to know if baricitinib combined with remdesivir can prevent or reduce the hyper-inflammatory “cytokine storm” that can fatally overwhelm the lungs and other parts of the body in people with COVID-19 when their immune system reacts to coronavirus infection.

combining baricitinib with remdesivir may yield an even more effective treatment option for people most severely affected by this illness

The ACTT-1 trial was carried out in 60 trial sites around the globe, in which treatment with remdesivir was compared with placebo. Remdesivir was administered intravenously as a 200-mg loading dose on day 1, followed by a 100-mg maintenance dose administered daily on days 2 through 10 or until hospital discharge or death.  Preliminary results from the trial published in the New England Journal of Medicine showed that patients with COVID-19 who received remdesivir recovered in 11 days on average compared to 15 days for patients in the placebo group – a statistically significant improvement. 

Second stage of the trial (ACTT-2), is now studying remdesivir in combination with baricitinib or placebo in a double-blind, randomized trial, for people hospitalized with severe COVID-19 infection. All patients will receive remdesivir intravenously for up to 10 days. Half of the patients will also be given baricitinib by mouth, with the remaining half receiving an identical placebo, both for up to 14 days.

“What concerns us is that in some people the immune response to coronavirus can be more deadly than the infection itself, and there is no known treatment for this yet,” said Barry Zingman, M.D., professor of medicine at Einstein and clinical director, infectious diseases, at the Moses division of Montefiore Health System. “Including baricitinib in our trial may reduce COVID-19-related inflammation and combining baricitinib with remdesivir may yield an even more effective treatment option for people most severely affected by this illness.” Dr. Zingman oversaw the original remdesivir study at Montefiore and is directing ACTT-2.

Both trials are sponsored by the National  Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.