International Collaboration To Fast-Track Trials Of Several Drugs For COVID-19 Treatment Formed

On April 9, President Donald Trump announced that ten drugs were being studied in clinical trials in the United States to quickly find a remedy to the unprecedented situation. This process is generally a lengthy one as it takes around 12 years for the Food and Drugs Administration (FDA)’s official approval if they follow the conventional steps. 

Hence, an international collaboration initiated by University of Pittsburgh's School of Medicine was launched at the University of Pittsburgh Medical Center (UPMC) on April 4. "The solution is to find an optimal tradeoff between doing something now, such as prescribing a drug off-label, or waiting until traditional clinical trials are complete," Derek Angus, MD, and MPH, professor and chair, Department of Critical Care Medicine at Pitt and UPMC said in the news release.

What The Collaboration Wants To Achieve

REMAP-Community Acquired Pneumonia (REMAP-CAP) is an old platform established in 2015 to discover effective treatments for severe pneumonia. Back then, Angus and his colleagues wrote about this development in the Journal of the American Medical Association explaining its design that can be applicable to both pandemics and regular life-threatening scenarios. 

Once the COVID-19 infection spread, REMAP (randomized, embedded, multi-factorial, adaptive platform) was adapted by doctors with updated regimens to fight SARS-CoV-2. A study was published in Annals of the American Thoracic Society (AnnalsATS) on April 8 detailing how REMAP can rapidly assess various treatment options at the same time. They hypothesized that it could be done at a cheaper price with less patients, compared to prolonged clinical trials with multiple phases. 

Coronavirus COVID-19 Laboratory Test, Cure, Vaccine Andressa Parreiras, Biomedic, and Larissa Vuitika, biologist, work in a laboratory during the extraction of the virus genetic material on March 24, 2020 in Belo Horizonte, Brazil. The Ministry of Health convened The Technological Vaccine Center of the Federal University of Minas Gerais laboratory to conduct research on the coronavirus (COVID-19) in order to diagnose, test and develop a vaccine. According to the Ministry of Health, as of Tuesday, March 24, Brazil has 1.891 confirmed cases of the coronavirus (COVID-19) and at least 34 recorded deceases. Pedro Vilela/Getty Images

"Adaptive platform trials are rapidly being endorsed by the U.S. Food and Drug Administration, the Bill & Melinda Gates Foundation and others as a long-needed revolution in clinical trials," Angus explained. 

In January, REMAP-CAP started enrolling patients for this clinical trial in 13 countries across three continents, in altogether 52 ICUs. Some of the countries are in North America, Europe, Australia and New Zealand. After which, the outbreak transitioned into a pandemic and was adapted to the escalating situation in February. On the day of the launch, the UPMC-REMAP-COVID19 was started in the 40-hospital system as part of the initiative.  

Apart from the standard treatment offered at the medical facilities, patients additionally receive between one to three treatment options. Different combinations should be tested at the same time: the major options include hydroxychloroquine, steroids and immunomodulators. In case doctors find that a new drug has potential, they have to make adjustments to the existing platform, as opposed to starting a new trial afresh which could take longer.    

“The trial randomized patients to multiple interventions within 4 treatment domains: antibiotics, antiviral therapy for influenza, host immunomodulation with extended macrolide therapy, and alternative corticosteroid regimens, representing 240 treatment regimens,” the researchers explained in the paper.

The medication administered to the patients is checked on the basis of a 90-day mortality threshold. “The trial generates estimates of superiority, inferiority and equivalence between regimens on the primary outcome of 90-day mortality, stratified by presence or absence of concomitant shock and proven or suspected influenza infection,” the researchers said. The trial also compares strategies to provide ventilation and tries to find solutions to the respiratory infections affecting patients suffering from COVID-19.