无法手术肢体缺血患者重复动脉内输注骨髓单核细胞的效果：随机、双盲、安慰剂对照的经皮动脉内补充（ Juventas ）试验中再生内皮祖细胞。

Effect of repetitive intra-arterial infusion of bone marrow mononuclear cells in patients with no-option limb ischemia: the randomized, double-blind, placebo-controlled Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial.

机构信息

From Department of Nephrology & Hypertension (M.T., M.C.V.), Department of Vascular Surgery (M.T., F.L.M.), Department of Radiology (R.W.S., W.P.Th.M.M.), Van Creveldkliniek/Department of Hematology (R.E.G.S.), Cell Therapy Facility/ Department of Clinical Pharmacy (I.C.M.S.-C.), Julius Center for Health Sciences and Primary Care (Y.v.d.G., A.A., I.v.d.T.), Brain Center Rudolf Magnus, Department of Neurology and Neurosurgery (A.A.), and Department of Cardiology (P.A.D.), University Medical Center Utrecht, The Netherlands.

出版信息

Circulation. 2015 Mar 10;131(10):851-60. doi: 10.1161/CIRCULATIONAHA.114.012913. Epub 2015 Jan 7.

DOI:10.1161/CIRCULATIONAHA.114.012913

PMID:25567765

Abstract

BACKGROUND

Patients with severe limb ischemia may not be eligible for conventional therapeutic interventions. Pioneering clinical trials suggest that bone marrow-derived cell therapy enhances neovascularization, improves tissue perfusion, and prevents amputation. The objective of this trial was to determine whether repetitive intra-arterial infusion of bone marrow mononuclear cells (BMMNCs) in patients with severe, nonrevascularizable limb ischemia can prevent major amputation.

METHODS AND RESULTS

The Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) trial is a randomized, double-blind, placebo-controlled clinical trial in 160 patients with severe, nonrevascularizable limb ischemia. Patients were randomly assigned to repetitive (3 times; 3-week interval) intra-arterial infusion of BMMNC or placebo. No significant differences were observed for the primary outcome, ie, major amputation at 6 months, with major amputation rates of 19% in the BMMNC versus 13% in the placebo group (relative risk, 1.46; 95% confidence interval, 0.62-3.42). The safety outcome (all-cause mortality, occurrence of malignancy, or hospitalization due to infection) was not significantly different between the groups (relative risk, 1.46; 95% confidence interval, 0.63-3.38), neither was all-cause mortality at 6 months with 5% versus 6% (relative risk, 0.78; 95% confidence interval, 0.22-2.80). Secondary outcomes quality of life, rest pain, ankle-brachial index, and transcutaneous oxygen pressure improved during follow-up, but there were no significant differences between the groups.

CONCLUSIONS

Repetitive intra-arterial infusion of autologous BMMNCs into the common femoral artery did not reduce major amputation rates in patients with severe, nonrevascularizable limb ischemia in comparison with placebo. The general improvement in secondary outcomes during follow-up in both the BMMNC and the placebo group, as well, underlines the essential role for placebo-controlled design of future trials.

CLINICAL TRIAL REGISTRATION URL

http://www.clinicaltrials.gov. Unique identifier: NCT00371371.

摘要

背景

严重肢体缺血的患者可能不符合传统治疗干预的条件。开创性的临床试验表明，骨髓源性细胞疗法可增强新生血管形成、改善组织灌注并预防截肢。本试验的目的是确定在严重不可再血管化肢体缺血的患者中，重复动脉内输注骨髓单个核细胞（BMMNC）是否可以预防主要截肢。

方法和结果

通过经皮动脉内补充（JUVENTAS）的再生活跃内皮祖细胞试验是一项针对 160 例严重不可再血管化肢体缺血患者的随机、双盲、安慰剂对照临床试验。患者被随机分配至重复（3 次；3 周间隔）动脉内输注 BMMNC 或安慰剂。主要结局（6 个月时的主要截肢）无显著差异，BMMNC 组的主要截肢率为 19%，安慰剂组为 13%（相对风险，1.46；95%置信区间，0.62-3.42）。两组之间的安全性结局（全因死亡率、恶性肿瘤发生或因感染住院）无显著差异（相对风险，1.46；95%置信区间，0.63-3.38），6 个月时的全因死亡率也无显著差异，分别为 5%和 6%（相对风险，0.78；95%置信区间，0.22-2.80）。次要结局（生活质量、静息痛、踝肱指数和经皮氧分压）在随访期间得到改善，但两组之间无显著差异。