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: hernioplasty; herniorrhaphy; opioid use; pain.

Figures

Figure 1

CONSORT flow diagram for study 1 and study 2. Note: ITT consists of all randomized patients who had at least two visual analog scale pain intensity scores. Abbreviation: ITT, intent-to-treat population.

Figure 2

SPI for study 1, study 2, and pooled dataset through 24, 48, and 72 hours. Note: *Statistically significant (P ≤ 0.05). Abbreviation: SPI, summed pain intensity.

Figure 3

TOpA for study 1, study 2, and pooled dataset through 24, 48, and 72 hours. Note: *Statistically significant (P ≤ 0.05). Abbreviation: TOpA, total opioid analgesia.

Figure 4

I-SPI-TOpA through 24, 48, and 72 hours, study 1, study 2, and pooled dataset. Note: *Statistically significant (P ≤ 0.05). Abbreviations: I-SPI-TOpA, integrated SPI and TOpA variable; SPI, summed pain intensity; TOpA, total use of opioid analgesia.