Trial shows two investigational drugs are ineffective for treating severe COVID-19
Despite the success of vaccines for preventing COVID-19, and of drugs for treating the disease, outcomes for severely ill patients admitted to the hospital remains poor. Identifying new therapies for severe COVID-19 remains a high priority and one in which Vanderbilt University Medical Center is taking a leading role.
A study published April 11 in the Journal of the American Medical Association (JAMA) evaluated two drugs that act on the renin-angiotensin system (RAS) as potential treatments for severe COVID-19. Severe acute respiratory syndrome coronavirus2 (SARS-CoV-2), the virus that causes COVID-19, enters pulmonary and myocardial cells through binding of its spike protein to the human angiotensin-converting enzyme 2 (ACE2). ACE2 is a vital enzyme that controls blood pressure and blood flow to multiple organs, including the lungs, heart and kidneys.
A prevailing hypothesis since early in the COVID-19 pandemic is that viral binding to ACE2 inhibits the conversion of angiotensin II (ANG II) to angiotensin 1-7 (ANG 1-7), thereby causing a pathological imbalance in the RAS, favoring the ANG II pathway, promoting inflammation, constriction of the blood vessels and thrombosis (blood clots). Thus, these RAS changes may be central to the development of severe clinical effects in the lungs and other organs.
VUMC led two blinded, placebo-controlled multicenter randomized clinical trials evaluating two investigational drugs aimed at regulating the RAS during SARS-CoV-2 infection. These two agents work in different ways to balance the Ang II to ANG (1-7) ratio. TRV-027 is a biased ligand acting on the angiotensin II receptor, while TXA-127 is synthetic angiotensin (1-7).
The trials demonstrated that neither drug was effective for treating severe COVID-19.
