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

Alexander J. Robbins; Nur Amamlina 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

doi:10.1111/bcp.15618

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

Alexander J. Robbins^*, Nur Amamlina 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 SzydloJoseph Boyle, Katrina M. Pollock, David Owen

^*Corresponding author for this work

Cancer Clinical Trials Unit

Research output: Contribution to journal › Article › peer-review

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 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.

Original language	English
Pages (from-to)	1495-1501
Number of pages	7
Journal	British Journal of Clinical Pharmacology
Volume	89
Issue number	4
Early online date	27 Nov 2022
DOIs	https://doi.org/10.1111/bcp.15618
Publication status	Published - Apr 2023

Bibliographical note

Funding Information:
This work was supported by the British Heart Foundation grant RE/18/4/34215, by Trevena Inc. and by Imperial College London COVID‐19 research fund. Funding information

Publisher Copyright:
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Keywords

clinical trials
coagulation
randomized controlled trial

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

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Robbins, A. J., Che Bakri, N. A., 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., ... Owen, D. (2023). The effect of TRV027 on coagulation in COVID-19: A pilot randomized, placebo-controlled trial. British Journal of Clinical Pharmacology, 89(4), 1495-1501. https://doi.org/10.1111/bcp.15618

@article{0c85dcf0131a46058bef820308759793,

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

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 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.",

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author = "Robbins, {Alexander J.} and {Che Bakri}, {Nur Amamlina} and Edward Toke-Bjolgerud and Aaron Edwards and Asha Vikraman and Cathy Michalsky and Michael Fossler and Lemm, {Nana Marie} and Savviz Medhipour and William Budd and Athanasia Gravani and Lisa Hurley and Vikas Kapil and Aimee Jackson and Dagan Lonsdale and Victoria Latham and Michael Laffan and Neil Chapman and Nichola Cooper and Richard Szydlo and Joseph Boyle and Pollock, {Katrina M.} and David Owen",

note = "Funding Information: This work was supported by the British Heart Foundation grant RE/18/4/34215, by Trevena Inc. and by Imperial College London COVID‐19 research fund. Funding information Publisher Copyright: {\textcopyright} 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.",

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month = apr,

doi = "10.1111/bcp.15618",

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Robbins, AJ, Che Bakri, NA, Toke-Bjolgerud, E, Edwards, A, Vikraman, A, Michalsky, C, Fossler, M, Lemm, NM, 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 2023, 'The effect of TRV027 on coagulation in COVID-19: A pilot randomized, placebo-controlled trial', British Journal of Clinical Pharmacology, vol. 89, no. 4, pp. 1495-1501. https://doi.org/10.1111/bcp.15618

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AU - Robbins, Alexander J.

AU - Che Bakri, Nur Amamlina

AU - Toke-Bjolgerud, Edward

AU - Edwards, Aaron

AU - Vikraman, Asha

AU - Michalsky, Cathy

AU - Fossler, Michael

AU - Lemm, Nana Marie

AU - Medhipour, Savviz

AU - Budd, William

AU - Gravani, Athanasia

AU - Hurley, Lisa

AU - Kapil, Vikas

AU - Jackson, Aimee

AU - Lonsdale, Dagan

AU - Latham, Victoria

AU - Laffan, Michael

AU - Chapman, Neil

AU - Cooper, Nichola

AU - Szydlo, Richard

AU - Boyle, Joseph

AU - Pollock, Katrina M.

AU - Owen, David

N1 - Funding Information: This work was supported by the British Heart Foundation grant RE/18/4/34215, by Trevena Inc. and by Imperial College London COVID‐19 research fund. Funding information Publisher Copyright: © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

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N2 - 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.

AB - 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.

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JO - British Journal of Clinical Pharmacology

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ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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