背景:通常使用痰定量聚合酶链反应(qPCR)在COPD中检测到高水平的爱泼斯坦-巴尔病毒(EBV),而气道免疫组织化学分析显示EBV检测在严重疾病中很常见。
目的:伐昔洛韦对COPD患者EBV抑制安全有效吗?
方法:COPD患者EB病毒抑制试验是一项随机试验,双盲,在贝尔法斯特Mater医院进行的安慰剂对照试验,北爱尔兰。符合条件的患者患有稳定的中度至重度COPD和痰EBV(使用qPCR测量),并被随机分配(1:1)伐昔洛韦(1gtid)或匹配的安慰剂8周。主要疗效结果是在第8周时痰EBV抑制(定义为痰病毒载量减少≥90%)。主要安全性结果是严重不良反应的发生率。次要结果指标是FEV1和药物耐受性。探索性结果包括生活质量的变化,痰细胞计数,和细胞因子计数。
结果:从2018年11月2日至2020年3月12日,随机分配84例患者(n=43,伐昔洛韦)。81例患者完成了试验随访,并纳入了主要结局的意向治疗分析。伐昔洛韦组更多的参与者实现了EBV抑制(n=36[87.8%]vsn=17[42.5%];P<.001)。与安慰剂相比,伐昔洛韦与痰EBV滴度显着降低相关(-90,404拷贝/mL[IQR,-298,000至-15,200拷贝/mL]与-3,940拷贝/mL[IQR,-114,400至50,150拷贝/mL];P=.002)。伐昔洛韦组显示24-mLFEV1数值增加(差异,-44毫升[95%CI,-150至62毫升];P=.41)。然而,与安慰剂组相比,伐昔洛韦组的痰白细胞计数减少(差异,2.89[95%CI,1.5×106-7.4×106];P=.003)。
结论:伐昔洛韦对于COPD患者EBV抑制是安全有效的,并且可以减轻痰中炎性细胞浸润。当前研究的结果为评估长期临床结果的更大试验提供了支持。
背景:ClinicalTrials.gov;编号。:NCT03699904;URL:www。
结果:政府。
Epstein-Barr virus (EBV) frequently is measured at high levels in COPD using sputum quantitative polymerase chain reaction, whereas airway immunohistochemistry analysis has shown EBV detection to be common in severe disease.
Is
valaciclovir safe and effective for EBV suppression in COPD?
The Epstein-Barr Virus Suppression in COPD (EViSCO) trial was a randomized double-blind placebo-controlled trial conducted at the Mater Hospital Belfast, Northern Ireland. Eligible patients had stable moderate-to-severe COPD and sputum EBV (measured using quantitative polymerase chain reaction) and were assigned randomly (1:1) to valaciclovir (1 g tid) or matching placebo for 8 weeks. The primary efficacy outcome was sputum EBV suppression (defined as ≥ 90% sputum viral load reduction) at week 8. The primary safety outcome was the incidence of serious adverse reactions. Secondary outcome measures were FEV1 and drug tolerability. Exploratory outcomes included changes in quality of life, sputum cell counts, and cytokines.
From November 2, 2018, through March 12, 2020, 84 patients were assigned randomly (n = 43 to
valaciclovir). Eighty-one patients completed trial follow-up and were included in the intention-to-treat analysis of the primary outcome. A greater number of participants in the
valaciclovir group achieved EBV suppression (n = 36 [87.8%] vs n = 17 [42.5%]; P < .001).
Valaciclovir was associated with a significant reduction in sputum EBV titer compared with placebo (-90,404 copies/mL [interquartile range, -298,000 to -15,200 copies/mL] vs -3,940 copies/mL [interquartile range, -114,400 to 50,150 copies/mL]; P = .002). A statistically nonsignificant 24-mL numerical FEV1 increase was shown in the valaciclovir group (difference, -44 mL [95% CI, -150 to 62 mL]; P = .41). However, a reduction in sputum white cell count was noted in the
valaciclovir group compared with the placebo group (difference, 2.89 [95% CI, 1.5 × 106-7.4 × 106]; P = .003).
Valaciclovir is safe and effective for EBV suppression in COPD and may attenuate the sputum inflammatory cell infiltrate. The findings from the current study provide support for a larger trial to evaluate long-term clinical outcomes.
ClinicalTrials.gov; No.: NCT03699904; URL: www.
gov.