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

Abstract

BackgroundXaraColl®, 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.MethodsWe 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.ResultsThrough 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).ConclusionXaraColl offers great potential for improving the management of postoperative pain and warrants further investigation in definitive clinical trials.

The pharmacokinetics and safety of an intraoperative bupivacaine-collagen implant (XaraColl&reg;) for postoperative analgesia in women following total abdominal hysterectomy

“…Thereafter, there is a slow release phase which can sustain the local concentrations and provide analgesia through at least 48 hours. Such a mechanism is consistent with results from our controlled efficacy trials that have demonstrated analgesia through 72 hours postoperatively in patients undergoing open inguinal hernioplasty and gynecological surgeries 3,4…”

“…Other products currently in development include Posidur ® (Durect Corporation, Cupertino, CA), an injectable viscous depot of bupivacaine based on sucrose acetate isobutyrate, and XaraColl ® (Innocoll Technologies, Athlone, Ireland) (Figure 1), a biodegradable and fully resorbable collagen-based matrix that is designed to release and deliver bupivacaine for local, sustained action at the site(s) of surgical trauma. Randomized controlled trials performed in women undergoing open gynecological surgery3 and in men undergoing hernioplasty4 have concluded that XaraColl is effective in reducing patient use of opioid analgesia and/or their pain intensity for up to 3 or 4 days postoperatively. The product also offers great versatility and is already proven suitable for use in laparoscopic surgery 5.…”

A feasibility study to investigate the use of a bupivacaine-collagen implant (XaraColl) for postoperative analgesia following laparoscopic surgery

“…Since this was not a controlled study, we compared values of TOpA and SPI with previously reported pooled data from two studies of men undergoing open inguinal hernioplasty who also had the benefit of receiving XaraColl for postoperative analgesia 9. After 24 hours, the mean TOpA for this laparoscopic study (19.3 mg) was very similar to the value from the pooled open hernioplasty studies (19.5 mg).…”

“…We have recently reported on the safety and efficacy of XaraColl, a bupivacaine-collagen implant, for postoperative analgesia in patients undergoing open inguinal hernioplasty9 and open gynecological surgery 10. From the results obtained, we concluded that XaraColl implanted intraoperatively was able to target and control visceral pain more efficiently than continuous perfusion of the surgical wound with bupivacaine for 72 hours postoperatively 10.…”

“…The product is implanted during surgery and releases bupivacaine for local, sustained action at the site(s) of surgical trauma, while maintaining low systemic levels well below the drug’s neurotoxicity and cardiotoxicity thresholds 8. Recently reported multicenter randomized controlled trials have suggested that XaraColl is safe and effective for reducing postoperative pain and/or patient need of opioid analgesics for up to 72 hours following a laparotomy procedure such as open hernioplasty9 or total abdominal hysterectomy 10. The primary aim of this study was to determine whether it was possible to implant and appropriately position XaraColl laparoscopically.…”