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

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.

Keywords:

• pain
• opioid use
• herniorrhaphy
• hernioplasty

Acknowledgments

We thank the following investigators and their study staff who enrolled patients in the studies: Todd Gerkin (Vital Research), Mark Hanley (East Coast Clinical Research Group), Laurence Kam (Memorial Hermann Memorial City Hospital), Johanna Knust (Northwest Surgeons/HealthFirst Medical Group), Tim Melson (Helen Keller Hospital and Eliza Coffee Memorial Hospital), Harold Minkowitz (Memorial Hermann Memorial City Medical Center), Dennis Riff (Advanced Clinical Research), Paul Siami (Welborn Clinic Research Center), Steven Wininger (Precision Trials), Peter Winkle (Advanced Clinical Research Institute), and Jonathan Yunis (Sarasota Memorial Hospital).

Disclosure

This study was fully funded by Innocoll Technologies, and was performed by Premier Research, which recruited and monitored the sites, managed the clinical databases, analyzed the data, and wrote the study reports. HSM and PW received research funding from Innocoll Technologies. MJ and SLC are paid consultants to Innocoll Technologies.