Mary Wilson
Well-known member
First published April 6, 2023.
doi:10.1136/ thorax-2022-219668
Lorraine Ware,1,2 Nima Soleymanlou,3 Danny Francis McAuley,4 Vicente Estrada,5George A Diaz,6 Peter Lacamera,7 Renee Kaste,3 Wansuk Choi,3 Abhya Gupta,8Tobias Welte9
ABSTRACT
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 ef cacy 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- ow 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 rst 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 rst 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 signi cant 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 ef cacy 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.
https://thorax.bmj.com/content/thoraxjnl/early/2023/04/06/thorax-2022-219668.full.pdf
doi:10.1136/ thorax-2022-219668
Lorraine Ware,1,2 Nima Soleymanlou,3 Danny Francis McAuley,4 Vicente Estrada,5George A Diaz,6 Peter Lacamera,7 Renee Kaste,3 Wansuk Choi,3 Abhya Gupta,8Tobias Welte9
ABSTRACT
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 ef cacy 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- ow 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 rst 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 rst 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 signi cant 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 ef cacy 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.
https://thorax.bmj.com/content/thoraxjnl/early/2023/04/06/thorax-2022-219668.full.pdf