Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis
Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis
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DOI：
10.1056/nejmoa020191
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发表时间：
2002-08-08
影响因子：
158.5
通讯作者：
de Pauw, B
中科院分区：
文献类型：
--
作者：
Herbrecht, R;Denning, DW;de Pauw, B
伏立康唑是一种广谱三唑类药物，对曲霉有活性。我们进行了一项随机试验，比较伏立康唑和两性霉素B作为侵袭性曲霉病的主要治疗方法。方法在这项随机、非盲法试验中，患者接受静脉注射伏立康唑（第1天每公斤体重6毫克两次，然后每天每公斤4毫克两次，持续至少7天），随后每天口服两次200毫克，或静脉注射两性霉素B去氧胆酸盐（每天每公斤1至1.5毫克）。如果初始治疗失败或患者对第一种药物不耐受，则允许使用其他许可的抗真菌治疗。完全或部分反应被认为是成功的结果。结果伏立康唑组144例、两性霉素B组133例明确或可能有曲霉病的患者接受了至少一剂治疗。大多数患者的基础疾病是异基因造血细胞移植、急性白血病或其他血液病。在第12周，伏立康唑组有52.8%的患者（完全缓解20.8%，部分缓解31.9%）和两性霉素B组有31.6%的患者（完全缓解16.5%，部分缓解15.0%；绝对差异为21.2个百分点；95%可信区间为10.4至32.9）。12周存活率伏立康唑组为70.8%，两性霉素B组为57.9%（风险比0.59；95%可信区间0.40 ~ 0.88）。伏立康唑治疗的患者明显减少了严重的药物相关不良事件，但短暂性视觉障碍在伏立康唑治疗中很常见（发生在44.8%的患者中）。结论在侵袭性曲霉病患者中，与标准的两性霉素B初始治疗方法相比，伏立康唑初始治疗的疗效更好，生存率更高，严重副作用更少。
Background Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis.Methods In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome.Results A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients).Conclusions In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.