TRPC6 inhibitor (BI 764198) to reduce risk and severity of ARDS due to COVID-19: a phase II randomised controlled trial.
Thorax
; 78(8): 816-824, 2023 Aug.
Article
in English
| MEDLINE | ID: covidwho-2286329
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 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.Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Respiratory Distress Syndrome
/
COVID-19
Type of study:
Cohort study
/
Experimental Studies
/
Observational study
/
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Thorax
Year:
2023
Document Type:
Article
Affiliation country:
Thorax-2022-219668
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