Tejaswini Kulkarni, Joel Santiaguel, Raminder Aul, Mark Harnett, Julie Krop, Michael C Chen, Camilla S Graham, Toby M Maher
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This study evaluated the safety and efficacy of deupirfenidone in PASC patients with respiratory complications.</p><p><strong>Methods: </strong>Global, double-blind, randomised placebo-controlled trial evaluating 750 mg deupirfenidone twice daily <i>versus</i> placebo for 3 months in PASC patients with respiratory complications following hospitalisation for acute COVID-19 infection severe enough to necessitate supplemental oxygen (NCT04652518).</p><p><strong>Results: </strong>185 patients were randomised and treated (95 with deupirfenidone, 90 with placebo), with 177 included in the modified intention-to-treat population. The mean age was 54.5 years, 62.7% were male and 10.7% had prior mechanical ventilation. The 6-min walk distance improved across both arms between baseline and day 91 (deupirfenidone 44.3 m (95% CI 24.8-63.8 m) <i>versus</i> placebo 48.8 m (95% CI 29.2-68.4 m); p=0.70). The most common treatment-emergent adverse events (TEAEs) for deupirfenidone <i>versus</i> placebo were nausea (9.5% <i>versus</i> 1.1%), upper abdominal discomfort (5.3% <i>versus</i> 2.2%) and dyspepsia (6.3% <i>versus</i> 1.1%). TEAEs leading to trial drug discontinuation were 11.6% for deupirfenidone and 4.4% for placebo. The proportion of discontinuations considered at least possibly related to treatment was 8.6% for deupirfenidone and 2.4% for placebo.</p><p><strong>Discussion: </strong>Most patients with PASC and respiratory complications showed significant improvement over 91 days irrespective of treatment assignment. 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引用次数: 0
摘要
简介：严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染（PASC）急性后后遗症呼吸道并发症的病理生理机制尚不清楚，但预计进行性肺纤维化的发生率很高。去吡非尼酮（LYT-100）是吡非尼酮的选择性氘化形式，保留抗纤维化和抗炎活性，但耐受性提高。本研究评估了德吡非尼酮治疗伴有呼吸系统并发症的PASC患者的安全性和有效性。方法：一项全球性、双盲、随机安慰剂对照试验，评估因急性COVID-19感染住院后出现呼吸系统并发症的PASC患者（NCT04652518），每日两次750mg去吡非尼酮与安慰剂的对比，持续3个月。结果：185名患者被随机分组并接受治疗（95名患者使用deupirfenidone， 90名患者使用安慰剂），其中177名患者被纳入改良意向治疗人群。平均年龄54.5岁，62.7%为男性，10.7%为既往机械通气患者。从基线到第91天，两组6分钟步行距离均有所改善(去匹非尼酮为44.3米（95% CI 24.8-63.8米），安慰剂为48.8米（95% CI 29.2-68.4米）；p = 0.70)。与安慰剂相比，deupirfenidone最常见的治疗不良事件（teae）是恶心（9.5%对1.1%）、上腹部不适（5.3%对2.2%）和消化不良（6.3%对1.1%）。deupir非尼酮组导致试验药物停药的teae为11.6%，安慰剂组为4.4%。被认为至少可能与治疗相关的停药比例在去吡非尼酮组为8.6%，安慰剂组为2.4%。讨论：大多数PASC和呼吸系统并发症的患者在91天内表现出显著的改善，与治疗分配无关。deupir非尼酮耐受性良好，teae发生率低，这支持了特发性肺纤维化患者的进一步研究。
Deupirfenidone (LYT-100) in post-acute sequelae of SARS-CoV-2 with respiratory complications.
Introduction: The pathophysiology of respiratory complications in post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is poorly understood, but a high incidence of progressive pulmonary fibrosis was anticipated. Deupirfenidone (LYT-100) is a selectively deuterated form of pirfenidone that retains antifibrotic and anti-inflammatory activity but with improved tolerability. This study evaluated the safety and efficacy of deupirfenidone in PASC patients with respiratory complications.
Methods: Global, double-blind, randomised placebo-controlled trial evaluating 750 mg deupirfenidone twice daily versus placebo for 3 months in PASC patients with respiratory complications following hospitalisation for acute COVID-19 infection severe enough to necessitate supplemental oxygen (NCT04652518).
Results: 185 patients were randomised and treated (95 with deupirfenidone, 90 with placebo), with 177 included in the modified intention-to-treat population. The mean age was 54.5 years, 62.7% were male and 10.7% had prior mechanical ventilation. The 6-min walk distance improved across both arms between baseline and day 91 (deupirfenidone 44.3 m (95% CI 24.8-63.8 m) versus placebo 48.8 m (95% CI 29.2-68.4 m); p=0.70). The most common treatment-emergent adverse events (TEAEs) for deupirfenidone versus placebo were nausea (9.5% versus 1.1%), upper abdominal discomfort (5.3% versus 2.2%) and dyspepsia (6.3% versus 1.1%). TEAEs leading to trial drug discontinuation were 11.6% for deupirfenidone and 4.4% for placebo. The proportion of discontinuations considered at least possibly related to treatment was 8.6% for deupirfenidone and 2.4% for placebo.
Discussion: Most patients with PASC and respiratory complications showed significant improvement over 91 days irrespective of treatment assignment. Deupirfenidone was well tolerated, with low rates of TEAEs, which supports further investigation in patients with idiopathic pulmonary fibrosis.
期刊介绍：
ERJ Open Research is a fully open access original research journal, published online by the European Respiratory Society. The journal aims to publish high-quality work in all fields of respiratory science and medicine, covering basic science, clinical translational science and clinical medicine. The journal was created to help fulfil the ERS objective to disseminate scientific and educational material to its members and to the medical community, but also to provide researchers with an affordable open access specialty journal in which to publish their work.
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