Editor's Corner Extended - COVID-19: In Translation
Given the rapidity with which efforts are being implemented in order to translate new scientific discoveries into clinical trials to find a treatment for COVD-19 patients, JACC: Basic to Translational Science has added an Editor's Corner Extended feature to our website that will allow us to provide our readers with important new updates to keep you informed about the most important developments in COVID-19 translational science. All of the links below are personally chosen and curated by Dr. Mann, and will be updated weekly with pertinent new information.
Weeky update - 4.27.2020
Adaptive COVID-19 Treatment Trial (ACTT) shows that Remdesivir accelerates recovery from advanced COVID-19
On April 29, the NIH disclosed the preliminary findings of the Adaptive COVID-19 Treatment Trial (ACTT), the first clinical trial in the United States to evaluate an experimental treatment for COVID-19 (NCT04280705). ACTT was designed as an adaptive, randomized, double-blind, placebo-controlled trial to evaluate the safety and efficacy of Remdesivir (and eventually other drugs) in hospitalized adults diagnosed with COVID-19. Remdesivir is a nucleoside analog that interferes with the action of viral RNA-dependent RNA polymerase (DOI:10.1016/j.jacbts.2020.04.003). COVID-19 patients were randomized to receive Remdesivir or placebo and assessed daily as an inpatient, as well as followed as an outpatient for up to 29 days. The primary outcome variable was time to recovery by day 29. An independent data and safety monitoring board (DSMB) met on April 27 to review data and shared their interim analysis with the ACTT study team. The DSMB noted that when compared with placebo Remdesivir-treated patients had a shorter time to recovery, which is an end point that is used frequently in influenza trials. Preliminary results from ACTT show that patients treated with Remdesivir had a 31% faster time to recovery than those who received placebo (p<0.001). For the Remdesivir treatment arm the median time to recovery was 11 days for patients treated when compared with 15 days for those who received placebo. There was a trend toward (p=0.059) improved survival in the Remdesivir treatment arm.
Commentary: While these results fall short of being a home run because of their preliminary nature, they represent the first scientific evidence that anti-viral agents can be utilized to treat COVID-19 patients, and thus represent an important win in the war against COVID-19. As noted in JACC: Basic to Translational Science (DOI: 10.1016/j.jacbts.2020.04.003), Remdesivir was effective against multiple types of coronaviruses in cell culture and a mouse model of SARS; however, it did not show an effect in patients with Ebola. Importantly, there are a number of ongoing studies worldwide with Remdesivir, so more robust information will be forthcoming in the future.
Read the entire findings here.
Weekly update - 4.20.2020
NIH issues guidelines for the treatment of COVID-19 patients
This COVID-19 treatment guideline is the first document to help guide clinicians who are on the front lines caring for patients with COVID-19. Because information is evolving quickly, this guideline will serve as a living document that is updated frequently. The guidelines cover the following areas: critical care management, therapeutic options under investigation, and the use of concomitant medications. This is the best current go-to source for health care workers who are treating COVID-19 patients.
Read the COVID-19 treatment guidelines here.
FDA issues warning about treatment of COVID-19 patients with hydroxychloroquine or chloroquine
The FDA just released a warning on the use of hydroxychloroquine or chloroquine in combination with azithromycin and other QT prolonging medicines, because of increasing reports of cardiac arrhythmias in treated patients. Both of these drugs are already are being studied in clinical trials for COVID-19 (DOI 10.1016/j.jacbts.2020.04.003), and were granted temporary use by the FDA for treatment of hospitalized SARS-CoV-2 patients through an Emergency Use Authorization pending the results in ongoing clinical trials. This FDA link provides important FAQs on the emergency use of hydroxychloroquine and chloroquine, as well as guidelines for initial evaluation and monitoring of patients using hydroxychloroquine or chloroquine. Given that both of these agents are available through a prescription, the likelihood of off-label use is extremely high during the COVID-19 pandemic. Accordingly, this link should provide a useful resource for health care workers who are treating COVID-19 patients.
Read the entire article here.
Recent publications related to COVID-19 in JACC: Basic to Translational Science
COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities
Bonnie Ky and Douglas L. Mann