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. <\/p>\n
A study published April 11 in the Journal of the American Medical Association (JAMA)<\/i> 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<\/a> and blood flow to multiple organs, including the lungs, heart and kidneys. <\/p>\n
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. <\/p>\n
VUMC led two blinded, placebo-controlled multicenter randomized clinical trials<\/a> 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). <\/p>\n
The trials demonstrated that neither drug<\/a> was effective for treating severe COVID-19. <\/p>\n
\u201cThe finding from these trials demonstrate that giving drugs that are designed to modulate the RAS in a way that would seem to counteract damage done by the virus are not helpful in very sick patients with COVID-19,\u201d said the study\u2019s first author, Wesley Self, MD, MPH, associate professor and vice chair of the Department of Emergency Medicine, Senior Vice President for Clinical Research and Deputy Director, Vanderbilt Institute for Clinical and Translational Research. <\/p>\n
\u201cThese results are disappointing in that we did not identify new drugs for patients suffering from COVID-19. But they are also important because we now understand that giving these drugs, which would seem very logical from a mechanistic perspective, should not be done,\u201d he said. <\/p>\n
\u201cWe hypothesized increased levels of ANG II may be responsible for some of the changes in the human body<\/a> due to COVID-19 infection,\u201d said Sean P. Collins, MD, MSci, professor of Emergency Medicine, study chair, and the paper\u2019s senior author. <\/p>\n
\u201cIf there\u2019s too much ANG II, blood vessels in the lungs start to constrict, resulting in not enough blood flow<\/a> to the lungs. This can lead to small blood clots<\/a> in the lungs resulting in inflammation. We know that ANG II does that and that COVID-19 patients express some of those abnormalities. So, the logical thinking has been there\u2019s too much ANG II in COVID-19, and we need to counteract these levels. However, the results from these two trials do not support this idea,\u201d he said. <\/p>\n
\u201cWe understand a lot better now that these simple fixes in this pathway aren\u2019t going to be effective,\u201d said Matthew S. Shotwell, Ph.D., the study\u2019s primary statistician and associate professor of Biostatistics. \u201cWe now are focusing on understanding why we saw the results we observed in these trials.\u201d <\/p>\n
Self said that blood collected from the patients participating in the trial will now be analyzed to measure proteins to understand more about the process. <\/p>\n
\u201cThe ACTIV-4 Host Tissue trial was created to rapidly assess therapies that could potentially alter the body\u2019s response to infection and support recovery,\u201d said Yves Rosenberg, MD, MPH, branch chief of the Atherothrombosis and Coronary Artery Disease branch, located within the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). \u201cWhile these two drugs were not effective, we answered a pivotal question and are hopeful another agent being studied in ACTIV-4 Host Tissue may be beneficial.\u201d<\/p>\n
More information:<\/strong> Citation<\/strong>: This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no 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 Read More<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[],"tags":[],"class_list":["post-290353","post","type-post","status-publish","format-standard","hentry"],"_links":{"self":[{"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/posts\/290353","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/comments?post=290353"}],"version-history":[{"count":0,"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/posts\/290353\/revisions"}],"wp:attachment":[{"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/media?parent=290353"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/categories?post=290353"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/healthmedicinet.com\/i\/wp-json\/wp\/v2\/tags?post=290353"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
Wesley H. Self et al, Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor\u2013Biased Ligand in Adults With COVID-19, JAMA<\/i> (2023). DOI: 10.1001\/jama.2023.3546<\/a><\/p>\n<\/p>\n
Trial shows two investigational drugs are ineffective for treating severe COVID-19 (2023, April 11)
retrieved 11 April 2023
from https:\/\/medicalxpress.com\/news\/2023-04-trial-drugs-ineffective-severe-covid-.html <\/p>\n
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