{"id":23841,"date":"2023-05-16T04:29:00","date_gmt":"2023-05-15T20:29:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=23841"},"modified":"2023-05-16T05:52:55","modified_gmt":"2023-05-15T21:52:55","slug":"jama%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9a%e9%87%87%e7%94%a8%e5%90%88%e6%88%90%e8%a1%80%e7%ae%a1%e7%b4%a7%e5%bc%a0%e7%b4%a01-7%e5%92%8c%e8%a1%80%e7%ae%a1%e7%b4%a7%e5%bc%a0%e7%b4%a0ii","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=23841","title":{"rendered":"[JAMA\u53d1\u8868\u8bba\u6587]\uff1a\u91c7\u7528\u5408\u6210\u8840\u7ba1\u7d27\u5f20\u7d20(1-7)\u548c\u8840\u7ba1\u7d27\u5f20\u7d20II\u76841\u578b\u53d7\u4f53\u504f\u5411\u914d\u4f53\u8c03\u8282\u80be\u7d20\u2014\u8840\u7ba1\u7d27\u5f20\u7d20\u7cfb\u7edf\u6cbb\u7597\u65b0\u51a0\u75c5\u6bd2\u611f\u67d3\u6210\u5e74\u60a3\u8005"},"content":{"rendered":"\n

Original Investigation <\/p>\n\n\n\n

April 11, 2023<\/p>\n\n\n\n

Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor\u2013Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials<\/h1>\n\n\n\n

Wesley H.\u00a0Self,\u00a0Matthew S.\u00a0Shotwell,\u00a0Kevin W.\u00a0Gibbs,\u00a0et al<\/h3>\n\n\n\n

JAMA.\u00a0<\/em>2023;329(14):1170-1182. doi:10.1001\/jama.2023.3546<\/h3>\n\n\n\n

Key Points<\/p>\n\n\n\n

Question<\/strong>  Among adults hospitalized with severe COVID-19, does treatment with synthetic angiotensin (1-7) (TXA-127) or an angiotensin II type 1 receptor\u2013biased ligand (TRV-027) improve clinical outcomes?<\/p>\n\n\n\n

Findings<\/strong>  In 2 placebo-controlled, randomized clinical trials, the number of days alive and free from supplemental oxygen during the 28 days after trial enrollment (oxygen-free days) was not significantly different from placebo for TXA-127 (adjusted odds ratio, 0.88) or TRV-027 (adjusted odds ratio, 0.74).<\/p>\n\n\n\n

Meaning<\/strong>  These findings do not support the hypothesis that pharmacological modulation of the renin-angiotensin system with exogenous administration of synthetic angiotensin (1-7) or blockade of the angiotensin II type 1 receptor results in clinical benefit for patients with severe COVID-19.<\/a><\/p>\n\n\n\n

Abstract<\/p>\n\n\n\n

Importance<\/strong>  Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology.<\/p>\n\n\n\n

Objective<\/strong>  To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor\u2013biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II.<\/p>\n\n\n\n

Design, Setting, and Participants<\/strong>  Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022.<\/p>\n\n\n\n

Interventions<\/strong>  A 0.5-mg\/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg\/h continuous intravenous infusion of TRV-027 for 5 days or placebo.<\/p>\n\n\n\n

Main Outcomes and Measures<\/strong>  The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient\u2019s status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension.<\/p>\n\n\n\n

Results<\/strong>  Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, \u22122.3 [95% CrI, \u22124.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, \u22122.4 [95% CrI, \u22125.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo.<\/p>\n\n\n\n

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Conclusions and Relevance<\/strong>  In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19.<\/p>\n\n\n\n

Trial Registration<\/strong>  ClinicalTrials.gov Identifier: NCT04924660<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

Original Investigation  April 11, 2023 R […]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[32,23],"tags":[],"_links":{"self":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23841"}],"collection":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=23841"}],"version-history":[{"count":1,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23841\/revisions"}],"predecessor-version":[{"id":23842,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=\/wp\/v2\/posts\/23841\/revisions\/23842"}],"wp:attachment":[{"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=23841"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=23841"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/csccm.org.cn\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=23841"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}