自体扩增脂肪来源干细胞治疗复杂性肛隐窝型肛瘘：一项 III 期随机临床试验（FATT1：肛瘘先进治疗试验 1）和长期评估。
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.
机构信息
Department of Surgery and Cell Therapy, La Paz University Hospital, Universidad Autonoma de Madrid, Hospital La Paz IdiPaz, Madrid, Spain.
出版信息
Dis Colon Rectum. 2012 Jul;55(7):762-72. doi: 10.1097/DCR.0b013e318255364a.
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.
CLINICAL TRIALS REGISTRATION
www.clinicaltrials.gov, identifier NCT00475410; Sponsor, Cellerix SA.
背景
自体脂肪来源干细胞可能为复杂性肛痿的治疗提供一种新方法。在成功完成 I 期和 II 期临床试验后，进行了 III 期临床试验以评估安全性和疗效。
设计
在这项多中心、随机、单盲、附加临床试验中，来自 19 个中心的 200 例成年患者被随机分配接受 2000 万干细胞（A 组，64 例）、2000 万脂肪源性干细胞加纤维蛋白胶（B 组，60 例）或纤维蛋白胶（C 组，59 例），以闭合内口。瘘管愈合定义为 MRI 示外口上皮化和收集物<2cm。如果 12 周时瘘管未愈合，则给予第二剂量（A、B 组 4000 万干细胞）。患者在 24-26 周（主要终点）和 1 年（长期随访）时进行评估。
结果
所有结果均根据“盲法评估者”评估。24-26 周时，A、B、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）。对在技术先驱中心治疗的亚组进行分析，24-26 周时的愈合率分别为 54.55%、83.33%和 18.18%（p<0.001）。未报告严重不良事件。
结论
在复杂性肛痿的治疗中，20 或 6000 万脂肪源性干细胞单独或联合纤维蛋白胶的剂量被认为是一种安全的治疗方法，在 6 个月时的愈合率约为 40%，在 1 年随访时的愈合率超过 50%。它与单独纤维蛋白胶相当。三组之间无统计学差异。
临床试验注册
www.clinicaltrials.gov，标识符 NCT00475410；赞助商，Cellerix SA。
Zotero 插件