Cowley Nicholas J, Owen Andrew, Shiels Sarah C, Millar Joanne, Woolley Rebecca, Ives Natalie, Osman Husam, Moss Paul, Bion Julian F
Institute of Clinical Sciences, University of Birmingham, Birmingham, England2Department of Anaesthesia and Intensive Care, Worcester Royal Hospital, Worcestershire Acute National Health Service Trust, Worcester, England.
Institute of Clinical Sciences, University of Birmingham, Birmingham, England3University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, England.
JAMA Intern Med. 2017 Jun 1;177(6):774-783. doi: 10.1001/jamainternmed.2017.0895.
Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness.
To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients.
DESIGN, SETTING, AND PARTICIPANTS: A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6.
Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n = 44).
Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug.
Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups.
Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression.
clinicaltrials.gov Identifier: NCT01503918.
超过半数的成年人群存在潜伏性巨细胞病毒（CMV）感染，在这些个体中，高达三分之一的人在危重症发作期间可能发生病毒再激活（即病毒在血液等体液中可检测到时）。
确定抗病毒治疗在危重症患者总体人群中预防CMV再激活是否安全有效。
设计、地点和参与者：一项单中心、开放标签、随机对照临床试验招募了124例CMV血清学阳性患者，这些患者于2012年1月1日至2014年1月31日期间在重症监护病房接受至少24小时的机械通气。所有患者的平均基线急性生理与慢性健康状况评分II为17.6。
患者被随机分配接受盐酸伐昔洛韦抗CMV预防治疗（n = 34）或低剂量盐酸缬更昔洛韦治疗（n = 46），持续长达28天以抑制病毒再激活，或分配至不进行干预的对照组（n = 44）。
在开始研究药物后的28天随访期内血液中首次出现CMV再激活的时间。
在该研究的124例患者中（46例女性和78例男性；平均[标准差]年龄为56.9[16.9]岁），对照组有12例患者血液中发生病毒再激活，而缬更昔洛韦组有1例患者，伐昔洛韦组有2例患者（联合治疗组与对照组相比：风险比为0.14；95%置信区间为0.04 - 0.50）。尽管该试验未设定评估临床终点的效能，但由于死亡率较高，伐昔洛韦组提前终止；到28天时，34例患者中有14例（41.2%）死亡，而在决定终止该组时，对照组37例患者中有5例（13.5%）死亡。其他安全性终点在各组间显示出相似的结果。
使用伐昔洛韦或低剂量缬更昔洛韦进行抗病毒预防可抑制危重症患者的CMV再激活。然而，鉴于较高的死亡率，如果要确定CMV抑制的临床疗效和安全性，则需要进行大规模试验。
clinicaltrials.gov标识符：NCT01503918。
