The effect of TRV027 on coagulation in COVID‐19: A pilot randomized, placebo‐controlled trial
Alexander J Robbins, Nur Amalina Che Bakri, Edward Toke‐bjolgerud, Aaron Edwards, Asha Vikraman, Cathy Michalsky, Michael Fossler, Nana‐marie Lemm, Savviz Medhipour, William Budd, Athanasia Gravani, Lisa Hurley, Vikas Kapil, Aimee Jackson, Dagan Lonsdale, Victoria Latham, Michael Laffan, Neil Chapman, Nichola Cooper, Richard Szydlo, Joseph Boyle, Katrina M Pollock, David Owen
British Journal of Clinical Pharmacology, doi:10.1111/bcp.15618
COVID-19 causes significant thrombosis and coagulopathy, with elevated D-dimer a predictor of adverse outcome. The precise mechanism of this coagulopathy remains unclear; one hypothesis is that loss of angiotensin-converting enzyme 2 activity during viral endocytosis leads to pro-inflammatory angiotensin-II accumulation, loss of angiotensin-1-7 and subsequent vascular endothelial activation. We undertook a double-blind randomized, placebo-controlled experimental medicine study to assess the effect of TRV027, a synthetic angiotensin-1-7 analogue on D-dimer in 30 patients admitted to hospital with COVID-19. The study showed a similar rate of adverse events in TRV027 and control groups. There was a numerical decrease in D-dimer in the TRV027 group and increase in D-dimer in the placebo group; however, this did not reach statistical significance (P = .15). A Bayesian analysis demonstrated that there was a 92% probability that this change represented a true drug effect.
COMPETING INTERESTS SUPPORTING INFORMATION Additional supporting information can be found online in the Supporting Information section at the end of this article.
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