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Bosentan for high-risk outpatients with COVID-19 infection: a randomized, double blind, placebo-controlled trial
Shaahin Shahbazi1, Zahra Vahdat Shariatpanahi2, Erfan Shahbazi3
1Department of Internal Medicine, Faculty of Medicine, Ilam University of Medical Sciences, Iran.
Insights
Bosentan, an endothelin receptor blocker, significantly reduced hospitalization and thromboembolic events in high-risk COVID-19 patients. Early treatment with bosentan may improve outcomes and prevent disease progression.
Area of Science:
- Cardiovascular Medicine
- Infectious Diseases
- Pharmacology
Background:
- COVID-19 is associated with endothelial activation and damage, potentially due to endothelin-1 over-secretion.
- Endothelial dysfunction plays a role in the severity and complications of COVID-19.
Purpose of the Study:
- To evaluate the efficacy of bosentan, an endothelin receptor blocker, in preventing disease progression in high-risk COVID-19 outpatients.
- To assess the impact of bosentan on hospitalization, death, and thromboembolic events in COVID-19 patients.
Main Methods:
- A randomized, placebo-controlled trial involving high-risk COVID-19 outpatients.
- Patients received either bosentan (62.5 mg twice daily) or placebo for 30 days, alongside standard treatment.
- Primary outcome was hospitalization or death within 15 days; secondary outcomes included thromboembolic events and 30-day mortality.
Main Results:
- Bosentan significantly reduced the primary outcome of hospitalization or death within 15 days (2.3% vs 11.5%, P=0.006).
- Thromboembolic events were significantly lower in the bosentan group (1% vs 8.7%, P=0.008).
- Patients receiving bosentan had significantly more hospital-free days (P=0.004).
Conclusions:
- Early administration of bosentan may be a beneficial therapeutic strategy for high-risk COVID-19 outpatients.
- Bosentan demonstrated a potential to prevent disease progression and reduce thromboembolic complications in COVID-19.
- The findings suggest endothelin receptor blockade as a promising approach in managing severe COVID-19.
Background:
The endothelium is supposedly activated and damaged in COVID-19 because of endothelin-1 over-secretion. This study evaluates the effect of bosentan as an endothelin receptor blocker on the progression of disease in high-risk outpatients with COVID-19 infection.
Methods:
From 15 December 2021 to 15 May 2022, high-risk outpatients were randomly assigned to receive bosentan, 62.5 mg or placebo twice daily from enrollment for 30 days. Both groups received standard medical treatment too. On day 30 of the trial, the patients underwent complete doppler ultrasound of the lower extremities to detect asymptomatic thromboembolic events. The primary outcome in this study was hospitalization or death from any cause within the first 15 days. Secondary outcomes included thromboembolic events, hospital-free days and death from any cause within 30 days after randomization (IRCT.ir, IRCT20211203053263N1).
Findings:
Basal characteristics of the two groups were similar. Primary outcomes occurred in 3 (2.3%) of the 129 patients in the bosentan group versus 15 (11.5%) of the 130 patients in the placebo group [risk difference: -9.2% (95% CI: -15.3 to -3.1), P = 0.006]. Median hospital-free days was significantly higher in the bosentan group (P = 0.004). A total of three deaths occurred and all were in the control group. Bosentan was associated with a nonsignificant reduction in mortality compared with placebo (P = 0.24). Thromboembolic events occurred in one (1%) of 97 patients in the bosentan group versus nine (8.7%) of 104 patients in the placebo group within 30 days after randomization [risk difference: -8.3% (95% CI: -14.4 to -2.2), P = 0.008].
Interpretation:
Early administration of bosentan may prevent disease progression and thromboembolic events in high-risk outpatients with COVID-19.
Funding:
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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