Autologous Expanded Adipose-Derived Stem Cells for the Treatment of Complex Cryptoglandular Perianal Fistulas: A Phase III Randomized Clinical Trial (FATT 1: Fistula Advanced Therapy Trial 1) and Long-term Evaluation
Autologous Expanded Adipose-Derived Stem Cells for the Treatment of Complex Cryptoglandular Perianal Fistulas: A Phase III Randomized Clinical Trial (FATT 1: Fistula Advanced Therapy Trial 1) and Long-term Evaluation
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DOI：
10.1097/dcr.0b013e318255364a
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发表时间：
2012-07-01
影响因子：
3.9
通讯作者：
Garcia-Olmo, D.
中科院分区：
文献类型：
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作者：
Herreros, M. D.;Garcia-Arranz, M.;Garcia-Olmo, D.
背景：自体脂肪源性干细胞可能是治疗复杂性肛瘘的一种新方法。在I期和II期临床试验成功后，进行III期临床试验以研究其安全性和有效性。设计：在这项多中心、随机、单盲、附加的临床试验中，来自19个中心的200名成年患者被随机分配接受2000万个干细胞A组64例，B组60例，C组59例。瘘管愈合定义为外部开口的上皮再形成和MRI显示不存在> 2cm的收集。如果瘘管在12周时没有愈合，则给予第二剂量（A组和B组中的4000万个干细胞）。在24 ~ 26周（主要终点）和1年（长期随访）时对患者进行评价。24 - 26周后，A、B和C组的愈合率分别为39.1%、43.3%和37.3%（p = 0.79）。1年时，愈合率分别为57.1%、52.4%和37.3%（p = 0.13）。在该技术的先锋中心治疗的亚群分析中，24 - 26周的愈合率分别为54.55%、83.33%和18.18%（p < 0.001）。结论：在治疗复杂性肛瘘时，单独使用2000万或6000万脂肪干细胞或与纤维蛋白胶联合使用被认为是安全的治疗方法，6个月时愈合率约为40%，1年随访时愈合率超过50%。其等同于单独的纤维蛋白胶。当比较3组时，未发现统计学显著差异。
BACKGROUND: Autologous adipose-derived stem cells may represent a novel approach for the management of complex fistula-in-ano. After successful phase I and II clinical trials, a phase III trial was performed to investigate the safety and efficacy.DESIGN: In this multicenter, randomized, single-blind, add-on clinical trial, 200 adult patients from 19 centers were randomly assigned to receive 20 million stem cells (group A, 64 patients), 20 million adipose-derived stem cells plus fibrin glue (group B, 60 patients), or fibrin glue (group C, 59 patients) after closure of the internal opening. Fistula healing was defined as reepithelization of the external opening and absence of collection >2 cm by MRI. If the fistula had not healed at 12 weeks, a second dose (40 million stem cells in groups A and B) was administered. Patients were evaluated at 24 to 26 weeks (primary end point) and at 1 year (long-term follow-up).RESULTS: All results are according to the "blinded evaluator" assessment. After 24 to 26 weeks, the healing rate was 39.1%, 43.3%, 37.3% in groups A, B, and C (p = 0.79). At 1 year, the healing rates were 57.1%, 52.4%, and 37.3 % (p = 0.13). On analysis of the subpopulation treated at the technique's pioneer center, healing rates were 54.55%, 83.33%, and 18.18%, at 24 to 26 weeks (p < 0.001). No SAEs were reported.CONCLUSIONS: In treatment of complex fistula-in-ano, a dose of 20 or 60 million adipose-derived stem cells alone or in combination with fibrin glue was considered a safe treatment, achieving healing rates of approximately 40% at 6 months and of more than 50% at 1-year follow-up. It was equivalent to fibrin glue alone. No statistically significant differences were found when the 3 groups where compared.