Early Administration of Bosentan in High-Risk COVID-19 Outpatients at Risk of Sarcopenia: A Randomized, Double-Blind, Placebo-Controlled Trial

IF 9.4 1区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Cachexia Sarcopenia and Muscle Pub Date : 2025-03-04 DOI:10.1002/jcsm.13753

Shaahin Shahbazi, Erfan Shahbazi, Farid Zayeri, Zahra Vahdat Shariatpanahi

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Abstract

Background

Endothelial damage induces myofibrillar breakdown and muscle degradation in COVID-19 infection. There is a relationship between increased endothelin-1 synthesis and sarcopenia. We evaluated the preventive effect of early bosentan therapy as an endothelin receptor blocker in sarcopenia in high-risk outpatients with COVID-19 infection.

Methods

From 15 December 2021 to 15 August 2023, patients within 3 days of the onset of signs and symptoms were randomly assigned to receive bosentan, 62.5 mg, or placebo, twice daily from enrollment for 30 days. The primary outcome was disease progression (death or hospitalization within 15 days after randomization), and the data for this outcome have been previously published. Sarcopenia as a secondary outcome was assessed prospectively at 3, 6, 9 and 12 months after randomization using the criteria of the Asian Working Group for Sarcopenia (AWGS) 2019 (IRCT.ir, IRCT20211203053263N1).

Results

A total of 313 patients (156 bosentan group, 157 controls) were included in the analyses, which were performed under the intent-to-treat principle. Overall, the incidence of sarcopenia was 8.6% (n = 27). Nineteen (73%) had severe sarcopenia. At the 3-month follow-up, the incidence of sarcopenia was 8.3% in the total population, with the significant risk difference (RD) of −10.17% in the bosentan group versus the control group. The incidence in the total population and RD in the bosentan group versus the control group at months 6, 9 and 12 were 8.6% (RD: −10.81%, p < 0.001), 8.3% (RD: −10.17%, p = 0.001) and 5.4% (RD: −6.99%, p = 0.003), respectively. During the study, 29 people developed severe COVID-19 and were hospitalized. At follow-up, sarcopenia occurred in four inpatients and 23 outpatients (p = 0.23). Mortality occurred in 5.1% (n = 16) of the total population, including 4 (1.3%) of the patients in the bosentan group and 12 (3.8%) of the patients in the placebo group (p = 0.069). None of the patients who died had sarcopenia. Bosentan did not cause any severe adverse events and was well tolerated.

Conclusion

Early administration of bosentan may prevent sarcopenia in high-risk outpatients with COVID-19.

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早期给予波生坦治疗有肌肉减少风险的高危COVID-19门诊患者：一项随机、双盲、安慰剂对照试验

背景内皮损伤在COVID-19感染中诱导肌纤维破裂和肌肉降解。内皮素-1合成增加与肌肉减少症之间存在关系。我们评估了早期波生坦治疗作为内皮素受体阻滞剂对COVID-19感染高危门诊患者肌肉减少症的预防作用。方法从2021年12月15日至2023年8月15日，患者在出现体征和症状后3天内随机分配接受波生坦、62.5 mg或安慰剂，每天两次，持续30天。主要结局是疾病进展（随机分组后15天内死亡或住院），该结局的数据此前已发表。在随机分组后的3、6、9和12个月，使用亚洲肌少症工作组（AWGS） 2019 （IRCT）的标准，对肌少症作为次要结局进行前瞻性评估。红外光谱、IRCT20211203053263N1)。结果313例患者（波生坦组156例，对照组157例）按照意向治疗原则纳入分析。总体而言，肌肉减少症的发生率为8.6% （n = 27）。19例（73%）有严重的肌肉减少症。在3个月的随访中，肌肉减少症的发生率在总人口中为8.3%，波生坦组与对照组的显著风险差异（RD）为- 10.17%。在第6、9和12个月，波生坦组与对照组的总发病率和RD分别为8.6% （RD:−10.81%,p < 0.001）、8.3% （RD:−10.17%,p = 0.001）和5.4% （RD:−6.99%,p = 0.003）。在研究期间，29人患上了严重的COVID-19并住院治疗。随访时，4例住院患者和23例门诊患者出现肌肉减少症（p = 0.23）。总死亡率为5.1% (n = 16)，其中波生坦组4例（1.3%），安慰剂组12例（3.8%）（p = 0.069）。所有死亡的病人都没有肌肉减少症。波生坦没有引起任何严重的不良事件，耐受性良好。结论早期给予波生坦可预防COVID-19高危门诊患者肌肉减少症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Cachexia Sarcopenia and Muscle MEDICINE, GENERAL & INTERNAL-

CiteScore

13.30

自引率

12.40%

发文量

234

审稿时长

16 weeks

期刊介绍： The Journal of Cachexia, Sarcopenia and Muscle is a peer-reviewed international journal dedicated to publishing materials related to cachexia and sarcopenia, as well as body composition and its physiological and pathophysiological changes across the lifespan and in response to various illnesses from all fields of life sciences. The journal aims to provide a reliable resource for professionals interested in related research or involved in the clinical care of affected patients, such as those suffering from AIDS, cancer, chronic heart failure, chronic lung disease, liver cirrhosis, chronic kidney failure, rheumatoid arthritis, or sepsis.