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

Alexander J Robbins^{1

2}, Nur Amalina Che Bakri^{2

3}, Edward Toke-Bjolgerud², Aaron Edwards¹, Asha Vikraman¹, Cathy Michalsky⁴, Michael Fossler⁴, Nana-Marie Lemm¹, Savviz Medhipour¹, William Budd¹, Athanasia Gravani¹, Lisa Hurley^{1

2}, Vikas Kapil⁵, Aimee Jackson⁶, Dagan Lonsdale^{7

8}, Victoria Latham², Michael Laffan⁹, Neil Chapman², Nichola Cooper¹⁰, Richard Szydlo⁹, Joseph Boyle^{2

11}, Katrina M Pollock¹, David Owen^{1

12}

Affiliations

¹ Imperial College Research Facility, Imperial College London, London, UK.
² Imperial College Healthcare NHS Trust, London, UK.
³ Department of Surgery and Cancer, Imperial College London, London, UK.
⁴ Trevena, Inc., Chesterbrook, Pennsylvania, USA.
⁵ William Harvey Research Institute, Centre for Cardiovascular Medicine and Devices, Faculty of Medicine and Dentistry, Queen Mary University London, London, UK.
⁶ Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
⁷ Department of Clinical Pharmacology, St George's University of London, London, UK.
⁸ Department of Critical Care, St George's University Hospitals NHS Foundation Trust, London, UK.
⁹ Centre for Haematology, Imperial College London, London, UK.
¹⁰ Department of Inflammation and Immunity, Imperial College London, London, UK.
¹¹ National Heart and Lung Institute, Imperial College London, London, UK.
¹² Department of Brain Sciences, Imperial College London, London, UK.

PMID: 36437688
PMCID: PMC10952550
DOI: 10.1111/bcp.15618

Randomized Controlled Trial

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

Alexander J Robbins et al. Br J Clin Pharmacol. 2023 Apr.

. 2023 Apr;89(4):1495-1501.

doi: 10.1111/bcp.15618. Epub 2022 Dec 14.

Authors

Affiliations

¹ Imperial College Research Facility, Imperial College London, London, UK.
² Imperial College Healthcare NHS Trust, London, UK.
³ Department of Surgery and Cancer, Imperial College London, London, UK.
⁴ Trevena, Inc., Chesterbrook, Pennsylvania, USA.
⁵ William Harvey Research Institute, Centre for Cardiovascular Medicine and Devices, Faculty of Medicine and Dentistry, Queen Mary University London, London, UK.
⁶ Cancer Research Clinical Trials Unit, University of Birmingham, Birmingham, UK.
⁷ Department of Clinical Pharmacology, St George's University of London, London, UK.
⁸ Department of Critical Care, St George's University Hospitals NHS Foundation Trust, London, UK.
⁹ Centre for Haematology, Imperial College London, London, UK.
¹⁰ Department of Inflammation and Immunity, Imperial College London, London, UK.
¹¹ National Heart and Lung Institute, Imperial College London, London, UK.
¹² Department of Brain Sciences, Imperial College London, London, UK.

PMID: 36437688
PMCID: PMC10952550
DOI: 10.1111/bcp.15618

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.

Keywords: clinical trials; coagulation; randomized controlled trial.

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Conflict of interest statement

K.P. and D.O. hold advisory positions on the Accelerating COVID‐19 therapeutic interventions and vaccines (ACTIV)‐4D) host tissue protocol development board, National Institute for Health, USA and on the Randomized, Embedded, Multifactorial Adaptive Platform trial for Community‐Acquired Pneumonia (REMAP‐CAP) ACE2 renin angiotensin system (RAS) domain protocol development board. C.M. and M.J.F. are employees of and hold stock in Trevena. All other authors declare no conflicts of interest.

References

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

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

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