临床试验的原理和设计，评估同种异体人心肌干细胞冠状动脉内输注治疗急性心肌梗死伴左心室功能障碍患者的安全性和有效性：随机多中心双盲对照 CAREMI 试验（急性心肌梗死后患者的心肌干细胞）。
Rationale and Design of a Clinical Trial to Evaluate the Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With Acute Myocardial Infarction and Left Ventricular Dysfunction: The Randomized Multicenter Double-Blind Controlled CAREMI Trial (Cardiac Stem Cells in Patients With Acute Myocardial Infarction).
机构信息
From the Department of Cardiology, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañon, Facultad de Medicina, Universidad Complutense, Centro de Investigación Biomédica en Red-Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain (R.S.-R., A.C.P., M.E.F.-S., R.Y., J. Bermejo, F.F.-A.); Coretherapix S.L.U./Tigenix Group, Madrid, Spain (L.R.B., I.P., M.M., I.G.); HLA et Medicine (HLA-MED), Hôpital Saint-Louis, Paris, France (R.A.-D., D.C.); Department of Cardiovascular Medicine, University Hospitals and KU Leuven, Belgium (P.C., J. Bogaert, S.J.); Department of Cardiac Surgery, Complejo Hospitalario de Navarra, Pamplona, Spain (R.S.); and Department of Development and Cardiovascular Repair, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain (A.B.).
出版信息
Circ Res. 2017 Jun 23;121(1):71-80. doi: 10.1161/CIRCRESAHA.117.310651. Epub 2017 May 22.
RATIONALE
Stem cell therapy has increased the therapeutic armamentarium in the fight against ischemic heart disease and heart failure. The administration of exogenous stem cells has been investigated in patients suffering an acute myocardial infarction, with the final aim of salvaging jeopardized myocardium and preventing left ventricular adverse remodeling and functional deterioration. However, phase I and II clinical trials with autologous and first-generation stem cells have yielded inconsistent benefits and mixed results.
OBJECTIVE
In the search for new and more efficient cellular regenerative products, interesting cardioprotective, immunoregulatory, and cardioregenerative properties have been demonstrated for human cardiac stem cells. On the other hand, allogeneic cells show several advantages over autologous sources: they can be produced in large quantities, easily administered off-the-shelf early after an acute myocardial infarction, comply with stringent criteria for product homogeneity, potency, and quality control, and may exhibit a distinctive immunologic behavior.
METHODS AND RESULTS
With a promising preclinical background, CAREMI (Cardiac Stem Cells in Patients With Acute Myocardial Infarction) has been designed as a double-blind, 2:1 randomized, controlled, and multicenter clinical trial that will evaluate the safety, feasibility, and efficacy of intracoronary delivery of allogeneic human cardiac stem cell in 55 patients with large acute myocardial infarction, left ventricular dysfunction, and at high risk of developing heart failure.
CONCLUSIONS
This phase I/II clinical trial represents a novel experience in humans with allogeneic cardiac stem cell in a rigorously imaging-based selected group of acute myocardial infarction patients, with detailed safety immunologic assessments and magnetic resonance imaging-based efficacy end points.
CLINICAL TRIAL REGISTRATION
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02439398.
背景
干细胞疗法在对抗缺血性心脏病和心力衰竭方面增加了治疗手段。已经在患有急性心肌梗死的患者中研究了外源性干细胞的给药，最终目的是挽救受损的心肌并防止左心室不良重塑和功能恶化。然而，自体和第一代干细胞的 I 期和 II 期临床试验的益处和结果不一致。
目的
在寻找新的、更有效的细胞再生产品的过程中，人类心脏干细胞表现出了有趣的心脏保护、免疫调节和心脏再生特性。另一方面，同种异体细胞相对于自体来源具有几个优势：它们可以大量生产，在急性心肌梗死后早期即可现成地给药，符合产品均一性、效力和质量控制的严格标准，并且可能表现出独特的免疫行为。
方法和结果
在有前途的临床前背景下，CAREMI（急性心肌梗死后患者的心脏干细胞）被设计为一项双盲、2:1 随机、对照和多中心临床试验，该试验将评估 55 例大面积急性心肌梗死、左心室功能障碍和心力衰竭高风险患者冠状动脉内给予同种异体人心肌干细胞的安全性、可行性和疗效。
结论
这项 I/II 期临床试验代表了在严格基于影像学选择的急性心肌梗死患者中使用同种异体心脏干细胞的人类的新经验，具有详细的安全性免疫评估和基于磁共振成像的疗效终点。
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