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The effect of TRV027 on coagulation in COVID 19: A pilot randomized, placebo-controlled controlled trial

Title: The effect of TRV027 on coagulation in COVID 19: A pilot randomized, placebo-controlled controlled trial
Authors: Robbins, AJ
Che Bakri, NA
Toke-Bjolgerud, E
Edwards, A
Vikraman, A
Michalsky, C
Fossler, M
Lemm, N-M
Medhipour, S
Budd, W
Gravani, A
Hurley, L
Kapil, V
Jackson, A
Lonsdale, D
Latham, V
Laffan, M
Chapman, N
Cooper, N
Szydlo, R
Boyle, J
Pollock, KM
Owen, D
Item Type: Journal Article
Abstract: 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 randomised, 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 (REC ref. 20/HRA/3414), Clinical Trial No. NCT04419610. 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=0.15). A Bayesian analysis demonstrated there was a 92% probability that this change represented a true drug effect.
Issue Date: Apr-2023
Date of Acceptance: 18-Nov-2022
URI: http://hdl.handle.net/10044/1/100559
DOI: 10.1111/bcp.15618
ISSN: 0306-5251
Publisher: British Pharmacological Society
Start Page: 1495
End Page: 1501
Journal / Book Title: British Journal of Clinical Pharmacology
Volume: 89
Issue: 4
Copyright Statement: © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publication Status: Published
Online Publication Date: 2022-11-27
Appears in Collections:Department of Immunology and Inflammation
Department of Infectious Diseases
National Heart and Lung Institute
Faculty of Medicine
Imperial College London COVID-19
Department of Brain Sciences

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