Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial.
Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial.
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DOI：
10.1001/jama.2012.28726
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发表时间：
2012-12-12
影响因子：
120.7
通讯作者：
Simari, Robert D.
中科院分区：
文献类型：
--
作者：
Traverse, Jay H.;Henry, Timothy D.;Pepine, Carl J.;Willerson, James T.;Zhao, David X. M.;Ellis, Stephen G.;Forder, John R.;Anderson, R. David;Hatzopoulos, Antonis K.;Penn, Marc S.;Perin, Emerson C.;Chambers, Jeffrey;Baran, Kenneth W.;Raveendran, Ganesh;Lambert, Charles;Lerman, Amir;Simon, Daniel I.;Vaughan, Douglas E.;Lai, Dejian;Gee, Adrian P.;Taylor, Doris A.;Cogle, Christopher R.;Thomas, James D.;Olson, Rachel E.;Bowman, Sherry;Francescon, Judy;Geither, Carrie;Handberg, Eileen;Kappenman, Casey;Westbrook, Lynette;Piller, Linda B.;Simpson, Lara M.;Baraniuk, Sarah;Loghin, Catalin;Aguilar, David;Richman, Sara;Zierold, Claudia;Spoon, Daniel B.;Bettencourt, Judy;Sayre, Shelly L.;Vojvodic, Rachel W.;Skarlatos, Sonia I.;Gordon, David J.;Ebert, Ray F.;Kwak, Minjung;Moye, Lemuel A.;Simari, Robert D.
虽然在以前的临床试验中已经评估了ST段心肌梗死（STEMI）后细胞治疗的递送，但在随机指定递送时间的试验中尚未分析细胞递送时间对左心室（LV）功能的影响。目的：确定1)STEMI后冠状动脉内自体骨髓单个核细胞（BMC）递送对整体和局部左室功能恢复的影响；2)BMC递送时间（再灌注后3天和7天）是否影响这种效果。2008年7月17日至2011年11月15日期间，120名患者被纳入国家心肺血液研究所（NHLBI）赞助的心血管细胞治疗研究网络（CCTRN）的随机、2×2因子、双盲、安慰剂对照试验，研究对象是在STEMI前路经皮冠状动脉介入治疗（PCI）成功后的左室功能障碍（左室射血分数(LVEF)≤45%）患者。冠状动脉内输注150 × 106个BMC或安慰剂（随机2:1 BMC：安慰剂），输注时间为12小时，并于pci术后第3天或第7天（随机1:1）进行处理。共同的主要终点是：1)心脏磁共振成像测量的6个月时梗死区和边界区整体（LVEF）和局部（壁运动）左室功能的变化；2)第3天和第7天治疗时间对左室功能的影响。次要终点包括主要不良心血管事件以及左室容积和梗死面积的变化。患者平均年龄56.9±10.9岁，男性占87.5%。6个月时，BMC组（45.2±10.6至48.3±13.3%）和安慰剂组（44.5±10.8至47.8±13.6%）的LVEF增加相似。在梗死区或边缘区均未观察到治疗对局部左室功能的影响。在第3天（- 0.9±2.9%,95% CI 6.6 ~ 4.9%, p=0.763）或第7天（1.1±2.9%,95% CI−4.7 ~ 6.9,p=0.702）治疗组间整体左室功能随时间变化的差异无统计学意义，两者之间也无差异。同时，治疗时间对局部左室功能恢复无明显影响。主要不良事件罕见，组间无差异。STEMI患者在事件发生后3天或7天成功接受首次PCI和冠状动脉内bmc治疗，其整体和局部左室功能恢复与安慰剂相似
While the delivery of cell therapy following ST segment myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular (LV) function has not been analyzed in a trial that randomly designated the time of delivery. To determine 1) the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery following STEMI on recovery of global and regional LV function and 2) if timing of BMC delivery (3 versus 7 days following reperfusion) influences this effect. Between July 17, 2008 and November 15, 2011, 120 patients were enrolled in a randomized, 2×2 factorial, double-blind, placebo-controlled trial of the National Heart, Lung, and Blood Institute (NHLBI)-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) of patients with LV dysfunction (LV Ejection Fraction (LVEF) ≤45%) following successful primary percutaneous coronary intervention (PCI) of anterior STEMI. Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1 BMC:placebo) within 12 hours of aspiration and processing administered at Day 3 or Day 7 (randomized 1:1) post-PCI. Co-primary endpoints were: 1) Change in global (LVEF) and regional (wall motion) LV function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and 2) Change in LV function as affected by timing of treatment on Day 3 versus Day 7. Secondary endpoints included major adverse cardiovascular events as well as changes in LV volumes and infarct size. Patient mean age was 56.9±10.9 years with 87.5% male. At 6 months, LVEF increased similarly in both BMC (45.2±10.6 to 48.3±13.3 %) and placebo groups (44.5±10.8 to 47.8±13.6 %). No detectable treatment effect on regional LV function was observed in either infarct or border zones. Differences between therapy groups in the change in global LV function over time when treated at Day 3 (−0.9±2.9%, 95% CI 6.6 to 4.9%, p=0.763) or Day 7 (1.1±2.9%, 95% CI −4.7 to 6.9, p=0.702) were not significant, nor were they different from each other. Also, timing of treatment had no detectable effect on recovery of regional LV function. Major adverse events were rare with no difference between groups. Patients with STEMI, who underwent successful primary PCI and administration of intra-coronary BMCs at either 3 or 7 days following the event, had recovery of global and regional LV function similar to placebo ClinicalTrials.gov Number, NCT00684021
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影响因子：
168.9
作者：
Makkar, Raj R.;Smith, Rachel R.;Cheng, Ke;Malliaras, Konstantinos;Thomson, Louise E. J.;Berman, Daniel;Czer, Lawrence S. C.;Marban, Linda;Mendizabal, Adam;Johnston, Peter V.;Russell, Stuart D.;Schuleri, Karl H.;Lardo, Albert C.;Gerstenblith, Gary;Marban, Eduardo
通讯作者：
Marban, Eduardo
影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
4.8
作者：
Traverse, Jay H.;Henry, Timothy D.;Simari, Robert D.
通讯作者：
Simari, Robert D.
影响因子：
168.9
作者：
Janssens, S;Dubois, C;Van de Werf, F
通讯作者：
Van de Werf, F
影响因子：
158.5
作者：
Schaechinger, Volker;Erbs, Sandra;Zeiher, Andreas M.
通讯作者：
Zeiher, Andreas M.