Hyperimmune IV Immunoglobulin Treatment A Multicenter Double-Blind Randomized Controlled Trial for Patients With Severe 2009 Influenza A(H1N1) Infection
Hyperimmune IV Immunoglobulin Treatment A Multicenter Double-Blind Randomized Controlled Trial for Patients With Severe 2009 Influenza A(H1N1) Infection
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DOI：
10.1378/chest.12-2907
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发表时间：
2013-08-01
期刊：
影响因子：
9.6
通讯作者：
Yuen, Kwok-Yung
中科院分区：
文献类型：
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作者：
Hung, Ivan F. N.;To, Kelvin K. W.;Yuen, Kwok-Yung
背景资料：流感大流行的经验表明，在症状发作后4 - 5天内给予恢复期血浆治疗可能有益。方法：这是一项多中心、前瞻性、双盲、随机对照试验。CSL Biotherapies（现为BioCSL）将从2009年甲型H1N1流感（A[H1N1]）感染中恢复的患者的恢复期血浆分离为超免疫IV免疫球蛋白（H-WIG）。接受标准抗病毒治疗、需要重症监护和辅助治疗的严重甲型H1N1流感感染患者随机接受H-WIG或2009年前生产的正常IV免疫球蛋白作为对照。结果：2010年至2011年，35例患者随机接受H-IVIG（17例）或IV免疫球蛋白（18例）。1例默认患者从分析中排除。未报告与治疗相关的不良事件。两组治疗前的基线人口统计学和病毒载量相似。连续的呼吸道病毒载量表明，与对照组相比，H-IVIG治疗与治疗后第5天和第7天显著较低的病毒载量相关（分别为P = 0.04和P = 0.02）。H-WIG组的初始血清细胞因子水平显著较高，但在治疗后3天降至相似水平。对22例在症状发作后5天内接受治疗的患者进行的亚组多变量分析表明，H-IVIG治疗是降低死亡率的唯一独立因素（OR，0.14; 95% CI，0.02-0.92; P = 0.04）。在症状发作5天内用H-IVIG治疗严重的A（H1N1）感染与较低的病毒载量和降低的死亡率相关ClinialTrials.gov。NCT01617317; URL：www.clinicaltrials.gov
Background: Experience from influenza pandemics suggested that convalescent plasma treatment given within 4 to 5 days of symptom onset might be beneficial. However, robust treatment data are lacking.Methods: This is a multicenter, prospective, double-blind, randomized controlled trial. Convalescent plasma from patients who recovered from the 2009 pandemic influenza A(H1N1) (A[H1N1]) infection was fractionated to hyperimmune IV immunoglobulin (H-WIG) by CSL Biotherapies (now BioCSL). Patients with severe A(H1N1) infection on standard antiviral treatment requiring intensive care and ventilatory support were randomized to receive H-WIG or normal IV immunoglobulin manufactured before 2009 as control. Clinical outcome and adverse effects were compared.Results: Between 2010 and 2011, 35 patients were randomized to receive H-IVIG (17 patients) or IV immunoglobulin (18 patients). One defaulted patient was excluded from analysis. No adverse events related to treatment were reported. Baseline demographics and viral load before treatment were similar between the two groups. Serial respiratory viral load demonstrated that H-IVIG treatment was associated with significantly lower day 5 and 7 posttreatment viral load when compared with the control (P = .04 and P = .02, respectively). The initial serum cytokine level was significantly higher in the H-WIG group but fell to a similar level 3 days after treatment. Subgroup multivariate analysis of the 22 patients who received treatment within 5 days of symptom onset demonstrated that H-IVIG treatment was the only factor that independently reduced mortality (OR, 0.14; 95% CI, 0.02-0.92; P = .04).Conclusions: Treatment of severe A(H1N1) infection with H-IVIG within 5 days of symptom onset was associated with a lower viral load and reduced mortality.Trial Registry: ClinialTrials.gov; No.: NCT01617317; URL: www.clinicaltrials.gov