Ann Intern Med. 2015 Jan 6;162(1):1-10. doi: 10.7326/M13-2729.
Optimal prevention of late cytomegalovirus (CMV) disease is poorly defined.
To compare valganciclovir prophylaxis with polymerase chain reaction-guided preemptive therapy.
Randomized, double-blind trial. (ClinicalTrials.gov: NCT00016068).
Multicenter trial.
184 recipients of hematopoietic cell transplantation (HCT) who were at high risk for late CMV disease (95 patients received valganciclovir and 89 received placebo).
6 months of valganciclovir (900 mg/d) or placebo. Patients with polymerase chain reaction positivity at 1000 copies/mL or greater or a 5-fold increase over baseline were treated with ganciclovir or valganciclovir (5 mg/kg or 900 mg twice daily, respectively).
The composite primary end point was death, CMV disease, or other invasive infections by 270 days after HCT. Secondary end points were CMV disease, CMV DNAemia, death, other infections, resource utilization, ganciclovir resistance, quality of life, immune reconstitution, and safety.
The primary composite outcome occurred in 20% of valganciclovir recipients versus 21% of placebo-preemptive therapy recipients (treatment difference, -0.01 [95% CI, -0.13 to 0.10]; P = 0.86). There was no difference in the primary end point or its components 640 days after HCT. The incidence of a CMV DNAemia level of 1000 copies/mL or greater or a 5-fold increase over baseline was reduced in the valganciclovir group (11% vs. 36%; P < 0.001). Neutropenia was not significantly different at the absolute neutrophil count of less than 0.5 × 109 cells/L (P = 0.57); however, more patients received hematopoietic growth factors in the valganciclovir group (25.3% vs. 12.4%; P = 0.026). No significant differences were seen in other secondary outcomes.
Some high-risk patients were not included.
Valganciclovir prophylaxis was not superior in reducing the composite end point of CMV disease, invasive bacterial or fungal disease, or death when compared with polymerase chain reaction-guided preemptive therapy. Both strategies performed similarly with regard to most clinical outcomes.
Roche Laboratories.
对于晚期巨细胞病毒（CMV）疾病的最佳预防措施尚未明确。
比较缬更昔洛韦预防与聚合酶链反应（PCR）指导下的抢先治疗。
随机、双盲试验。（ClinicalTrials.gov：NCT00016068）。
多中心试验。
184 例接受造血细胞移植（HCT）的患者，这些患者有发生晚期 CMV 疾病的高风险（95 例接受缬更昔洛韦治疗，89 例接受安慰剂治疗）。
6 个月的缬更昔洛韦（900 mg/d）或安慰剂。当患者的 PCR 检测结果为 1000 拷贝/mL 或更高，或基线时增加 5 倍时，给予更昔洛韦或缬更昔洛韦治疗（分别为 5 mg/kg 或 900 mg，每日 2 次）。
主要复合终点是移植后 270 天内的死亡、CMV 疾病或其他侵袭性感染。次要终点包括 CMV 疾病、CMV DNA 血症、死亡、其他感染、资源利用、更昔洛韦耐药、生活质量、免疫重建和安全性。
缬更昔洛韦组有 20%的患者发生主要复合结局，而安慰剂抢先治疗组有 21%的患者发生该结局（治疗差异，-0.01 [95%置信区间，-0.13 至 0.10]；P=0.86）。在 HCT 后 640 天，主要终点及其组成部分没有差异。缬更昔洛韦组的 CMV DNA 血症水平为 1000 拷贝/mL 或更高，或基线时增加 5 倍的发生率降低（11% vs. 36%；P<0.001）。中性粒细胞绝对计数（ANC）<0.5×109/L 的中性粒细胞减少症没有显著差异（P=0.57）；然而，缬更昔洛韦组有更多的患者接受了造血生长因子治疗（25.3% vs. 12.4%；P=0.026）。其他次要结局未见显著差异。
一些高危患者未被纳入。
与 PCR 指导的抢先治疗相比，缬更昔洛韦预防并未降低 CMV 疾病、侵袭性细菌或真菌感染或死亡的复合终点。两种策略在大多数临床结局方面表现相似。
罗氏公司。
