The effect of TRV027 on coagulation in COVID‐19: A pilot randomized, placebo‐controlled trial
et al., British Journal of Clinical Pharmacology, doi:10.1111/bcp.15618, COVRAS, NCT04419610, Dec 2022
Double-blind RCT 30 hospitalized COVID-19 patients in the United Kingdom showing a non-statistically significant trend towards decreased D-dimer levels with TRV027, an angiotensin-(1-7) analogue, compared to placebo. The trial was terminated early due to declining cases.
Standard of Care (SOC) for COVID-19 in the study country,
the United Kingdom, is very poor with very low average efficacy for approved treatments1.
The United Kingdom focused on expensive high-profit treatments, approving only one low-cost early treatment, which required a prescription and had limited adoption. The high-cost prescription treatment strategy reduces the probability of early treatment due to access and cost barriers, and eliminates complementary and synergistic benefits seen with many low-cost treatments.
|
risk of death, 73.3% higher, RR 1.73, p = 1.00, treatment 2 of 15 (13.3%), control 1 of 13 (7.7%).
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Robbins et al., 14 Dec 2022, Double Blind Randomized Controlled Trial, placebo-controlled, United Kingdom, peer-reviewed, 23 authors, trial NCT04419610 (history) (COVRAS).
Contact: alexander.robbins@nhs.net.
The effect of TRV027 on coagulation in COVID‐19: A pilot randomized, placebo‐controlled trial
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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Late treatment
is less effective
is less effective
