两项多中心、随机、双盲、安慰剂对照的初步研究中，XaraColl(®)（布比卡因-胶原植入物）用于术后镇痛的临床评估。

Clinical evaluation of XaraColl(®), a bupivacaine-collagen implant, for postoperative analgesia in two multicenter, randomized, double-blind, placebo-controlled pilot studies.

机构信息

Cusack Pharmaceutical Consulting, Burlington, NJ.

出版信息

J Pain Res. 2012;5:217-25. doi: 10.2147/JPR.S33453. Epub 2012 Jun 27.

DOI:10.2147/JPR.S33453

PMID:22792007

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3392712/

Abstract

BACKGROUND

XaraColl(®), a collagen-based implant that delivers bupivacaine to the site of surgical trauma, is under development for postoperative analgesia. Because of differing patient attitudes to postoperative pain control and the inability to assess baseline pain, standard clinical methods for evaluating analgesic efficacy are compromised and justify application of novel integrated approaches.

METHODS

We conducted two independent, multicenter, double-blind, placebo-controlled studies in men undergoing unilateral inguinal hernioplasty by open laparotomy to evaluate the safety and efficacy of XaraColl at different doses (100 mg and 200 mg of bupivacaine hydrochloride; study 1 and 2, respectively). Enrolled patients (50 in study 1 and 53 in study 2) were randomized to receive active or placebo implants in a 1:1 ratio. Postoperative pain intensity and use of supplementary opioid medication were recorded through 72 hours. Safety was assessed through 30 days. The principal efficacy variables were the summed pain intensity (SPI), total use of opioid analgesia (TOpA), and an integrated endpoint (I-SPI-TOpA). Each variable was analyzed at 24, 48, and 72 hours after implantation. A pooled analysis of both studies was also performed retrospectively.

RESULTS

Through 24 and 48 hours, XaraColl-treated patients experienced significantly less pain in study 1 (P < 0.001 and P = 0.012, respectively) whereas they took significantly less opioid analgesia in study 2 (P = 0.004 and P = 0.042, respectively). Over the same time intervals in the pooled analysis, treated patients experienced both significantly less pain (P < 0.001 and P = 0.006, respectively) and took significantly less opioid analgesia (P = 0.001 and P = 0.024, respectively). The I-SPI-TOpA endpoint that combined both SPI and TOpA demonstrated a significant treatment effect through 72 hours in the pooled analysis (P = 0.021).

CONCLUSION

XaraColl offers great potential for improving the management of postoperative pain and warrants further investigation in definitive clinical trials.

摘要

背景

XaraColl（®）是一种基于胶原蛋白的植入物，可将布比卡因递送至手术创伤部位，目前正在开发用于术后镇痛。由于患者对术后疼痛控制的态度不同，以及无法评估基线疼痛，因此标准的临床评估镇痛效果的方法受到影响，这证明需要应用新的综合方法。

方法

我们在接受单侧腹股沟疝修补术的男性中进行了两项独立的、多中心的、双盲、安慰剂对照研究，以评估 XaraColl 在不同剂量（分别为 100mg 和 200mg 盐酸布比卡因）下的安全性和疗效（研究 1 和研究 2）。纳入的患者（研究 1 为 50 例，研究 2 为 53 例）以 1:1 的比例随机接受活性或安慰剂植入物。通过 72 小时记录术后疼痛强度和补充阿片类药物的使用情况。通过 30 天评估安全性。主要疗效变量是总和疼痛强度（SPI）、总阿片类药物镇痛使用量（TOpA）和综合终点（I-SPI-TOpA）。每个变量在植入后 24、48 和 72 小时进行分析。还对两项研究进行了回顾性合并分析。

结果

在研究 1 中，与安慰剂组相比，XaraColl 治疗的患者在 24 小时（P < 0.001）和 48 小时（P = 0.012）时疼痛明显减轻，而在研究 2 中，XaraColl 治疗的患者在 24 小时（P = 0.004）和 48 小时（P = 0.042）时阿片类药物镇痛使用量明显减少。在合并分析的相同时间间隔内，治疗组患者的疼痛程度（P < 0.001 和 P = 0.006）和阿片类药物镇痛使用量（P = 0.001 和 P = 0.024）均明显减少。在合并分析中，综合 SPI 和 TOpA 的 I-SPI-TOpA 终点在 72 小时时显示出显著的治疗效果（P = 0.021）。