Related Experiment Video
Updated: Aug 4, 2025
Design of a Biocompatible Drug-Eluting Tracheal Stent in Mice with Laryngotracheal Stenosis
Published on: January 21, 2020
TRPC6 inhibitor (BI 764198) to reduce risk and severity of ARDS due to COVID-19: a phase II randomised controlled
Lorraine B Ware1,2, Nima Soleymanlou3, Danny Francis McAuley4
1Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA lorraine.ware@vanderbilt.edu.
Background:
Despite the availability of COVID-19 vaccinations, there remains a need to investigate treatments to reduce the risk or severity of potentially fatal complications of COVID-19, such as acute respiratory distress syndrome (ARDS). This study evaluated the efficacy and safety of the transient receptor potential channel C6 (TRPC6) inhibitor, BI 764198, in reducing the risk and/or severity of ARDS in patients hospitalised for COVID-19 and requiring non-invasive, supplemental oxygen support (oxygen by mask or nasal prongs, oxygen by non-invasive ventilation or high-flow nasal oxygen).
Methods:
Multicentre, double-blind, randomised phase II trial comparing once-daily oral BI 764198 (n=65) with placebo (n=64) for 28 days (+2-month follow-up).
Primary Endpoint:
proportion of patients alive and free of mechanical ventilation at day 29. Secondary endpoints: proportion of patients alive and discharged without oxygen (day 29); occurrence of either in-hospital mortality, intensive care unit admission or mechanical ventilation (day 29); time to first response (clinical improvement/recovery); ventilator-free days (day 29); and mortality (days 15, 29, 60 and 90).
Results:
No difference was observed for the primary endpoint: BI 764198 (83.1%) versus placebo (87.5%) (estimated risk difference -5.39%; 95% CI -16.08 to 5.30; p=0.323). For secondary endpoints, a longer time to first response (rate ratio 0.67; 95% CI 0.46 to 0.99; p=0.045) and longer hospitalisation (+3.41 days; 95% CI 0.49 to 6.34; p=0.023) for BI 764198 versus placebo was observed; no other significant differences were observed. On-treatment adverse events were similar between trial arms and more fatal events were reported for BI 764198 (n=7) versus placebo (n=2). Treatment was stopped early based on an interim observation of a lack of efficacy and an imbalance of fatal events (Data Monitoring Committee recommendation).
Conclusions:
TRPC6 inhibition was not effective in reducing the risk and/or severity of ARDS in patients with COVID-19 requiring non-invasive, supplemental oxygen support.
Trial Registration Number:
NCT04604184.
Related Concept Videos
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:21Acute Respiratory Failure-II
The underlying physiological abnormalities that contribute to hypoxemic respiratory failure include: