Duke University Medical Center and Duke Clinical Research Institute, Durham, NC, USA.
Ann Intern Med. 2010 Jun 15;152(12):761-9. doi: 10.7326/0003-4819-152-12-201006150-00003.
Cytomegalovirus (CMV) is the most prevalent opportunistic infection after lung transplantation. Current strategies do not prevent CMV in most at-risk patients.
To determine whether extending prophylaxis with oral valganciclovir from the standard 3 months to 12 months after lung transplantation is efficacious.
Randomized, clinical trial. Patients were randomly assigned by a central automated system to treatment or placebo. Patients and investigators were blinded to treatment status. (ClinicalTrials.gov registration number: NCT00227370)
Multicenter trial involving 11 U.S. lung transplant centers.
136 lung transplant recipients who completed 3 months of valganciclovir prophylaxis.
9 additional months of oral valganciclovir (n = 70) or placebo (n = 66).
The primary end point was freedom from CMV disease (syndrome or tissue-invasive) on an intention-to-treat basis 300 days after randomization. Secondary end points were CMV disease severity, CMV infection, acute rejection, opportunistic infections, ganciclovir resistance, and safety.
CMV disease occurred in 32% of the short-course group versus 4% of the extended-course group (P < 0.001). Significant reductions were observed with CMV infection (64% vs. 10%; P < 0.001) and disease severity (110 000 vs. 3200 copies/mL, P = 0.009) with extended treatment. Rates of acute rejection, opportunistic infections, adverse events, CMV UL97 ganciclovir-resistance mutations, and laboratory abnormalities were similar between groups. During the 6 months after study completion, a low incidence of CMV disease was observed in both groups.
Longer-term effects of extended prophylaxis were not assessed.
In adult lung transplant recipients who have received 3 months of valganciclovir, extending prophylaxis by an additional 9 months significantly reduces CMV infection, disease, and disease severity without increased ganciclovir resistance or toxicity. A beneficial effect with regard to prevention of CMV disease seems to extend at least through 18 months after transplantation.
巨细胞病毒（CMV）是肺移植后最常见的机会性感染。目前的策略并不能预防大多数高危患者的 CMV。
确定将肺移植后口服缬更昔洛韦的预防时间从标准的 3 个月延长至 12 个月是否有效。
随机临床试验。患者通过中央自动化系统随机分配至治疗组或安慰剂组。患者和研究人员对治疗情况不知情。（ClinicalTrials.gov 注册号：NCT00227370）
涉及 11 个美国肺移植中心的多中心试验。
136 名完成 3 个月缬更昔洛韦预防治疗的肺移植受者。
9 个月的口服缬更昔洛韦（n = 70）或安慰剂（n = 66）。
主要终点为随机分组后 300 天无 CMV 疾病（综合征或组织侵袭性）的比例。次要终点为 CMV 疾病严重程度、CMV 感染、急性排斥反应、机会性感染、更昔洛韦耐药和安全性。
短疗程组中有 32%发生 CMV 疾病，而长疗程组中仅有 4%（P < 0.001）。延长疗程治疗观察到 CMV 感染（64% vs. 10%；P < 0.001）和疾病严重程度（110000 拷贝/ml vs. 3200 拷贝/ml，P = 0.009）显著降低。两组急性排斥反应、机会性感染、不良事件、CMV UL97 更昔洛韦耐药突变和实验室异常的发生率相似。在研究结束后的 6 个月内，两组均观察到 CMV 疾病的低发生率。
未评估延长预防的长期效果。
在接受 3 个月缬更昔洛韦治疗的成人肺移植受者中，再延长 9 个月的预防治疗可显著降低 CMV 感染、疾病和疾病严重程度，而不会增加更昔洛韦耐药性或毒性。预防 CMV 疾病的效果似乎至少可延长至移植后 18 个月。
