Lotus Clinical Research, LLC, Pasadena, California, USA.
HD Research/First Surgical Hospital, Bellaire, Texas, USA.
Reg Anesth Pain Med. 2023 Dec;48(12):601-607. doi: 10.1136/rapm-2022-104110. Epub 2023 Apr 19.
Surgical site infiltration with bupivacaine hydrochloride (HCl) is a standard element of postoperative analgesia for soft tissue surgeries, but results in short-lived analgesia. A novel bupivacaine implant, XARACOLL (bupivacaine HCl), is Food and Drug Administration approved for treatment of acute postsurgical pain following adult inguinal herniorrhaphy. This study examined the efficacy and safety of the bupivacaine implant (300 mg) compared with placebo for postsurgical pain after abdominoplasty.
In this double-blind, placebo-controlled study, patients undergoing abdominoplasty were randomized to three 100 mg bupivacaine implants or three placebo collagen implants, in a 1:1 ratio, implanted intraoperatively. No other analgesics were administered into the surgical site. Patients were allowed opioids and acetaminophen for postoperative pain. Patients were followed for up to 30 days after treatment.
the analgesic effect of the bupivacaine implants through 24 hours postsurgery, measured by the sum of time-weighted pain intensity (SPI24). Prespecified key secondary outcomes included SPI48 and SPI72, percentage of opioid-free patients through 24, 48, and 72 hours, and adverse events, which were tested sequentially to control for multiplicity (ie, if the first variable failed to reach significance, no subsequent variables were declared statistically significant).
The bupivacaine implant patients (n=181) reported statistically significant lower SPI24 (mean (SD) SPI24=102 (43), 95% CI 95 to 109) compared with placebo patients (n=184; SPI24=117 (45), 95% CI 111 to 123, p=0.002). SPI48 was 190 (88, 95% CI 177 to 204) for INL-001 and 206 (96, 95% CI 192 to 219) for placebo, and not significantly different between groups. The subsequent secondary variables were therefore declared not statistically significant. SPI72 was 265 (131, 95% CI 244 to 285) for INL-001 and 281 (146, 95% CI 261 to 301) for placebo. The opioid-free percentage of patients at 24, 48, and 72 hours was 19%, 17%, and 17% for INL-001 and 6.5% for placebo patients (at all timepoints). The only adverse event occurring in ≥5% of patients and for which proportion INL-001 >placebo was back pain (7.7% vs 7.6%).
The study design was limited by not containing an active comparator. Compared with placebo, INL-001 provides postoperative analgesia that is temporally aligned with the period of maximal postsurgical pain in abdominoplasty and offers a favorable safety profile.
NCT04785625.
盐酸布比卡因（HCl）在软组织手术的术后镇痛中是一种标准的局部浸润方法，但只能提供短暂的镇痛效果。一种新型的布比卡因植入物 XARACOLL（HCl）已获得美国食品和药物管理局批准，用于治疗成人腹股沟疝修补术后的急性术后疼痛。本研究比较了布比卡因植入物（300mg）与安慰剂在腹部整形术后疼痛的疗效和安全性。
在这项双盲、安慰剂对照研究中，接受腹部整形术的患者以 1:1 的比例随机分为三组，每组接受 100mg 的布比卡因植入物或三组安慰剂胶原蛋白植入物，术中植入。手术部位未给予其他任何镇痛药。患者可使用阿片类药物和对乙酰氨基酚缓解术后疼痛。治疗后患者随访 30 天。
通过 24 小时术后时间加权疼痛强度（SPI24）测量布比卡因植入物的镇痛效果。预先设定的关键次要终点包括 SPI48 和 SPI72、24、48 和 72 小时无阿片类药物患者的百分比，以及不良事件，这些终点依次进行检验以控制多重性（即，如果第一个变量未达到显著水平，则不宣布随后的变量具有统计学意义）。
与安慰剂组（n=184；SPI24=117（45），95%CI 111 至 123，p=0.002）相比，布比卡因植入物组（n=181）患者报告的 SPI24 明显较低（平均值（SD）SPI24=102（43），95%CI 95 至 109）。SPI48 为 INL-001 组的 190（88，95%CI 177 至 204）和安慰剂组的 206（96，95%CI 192 至 219），两组之间无显著差异。因此，随后的次要变量被宣布不具有统计学意义。SPI72 为 INL-001 组的 265（131，95%CI 244 至 285）和安慰剂组的 281（146，95%CI 261 至 301）。24、48 和 72 小时无阿片类药物患者的百分比为 INL-001 组的 19%、17%和 17%，安慰剂组的 6.5%（所有时间点）。唯一发生在≥5%患者中且 INL-001 比例>安慰剂的不良事件是背痛（7.7%对 7.6%）。
该研究设计的局限性在于没有包含活性对照。与安慰剂相比，INL-001 提供了与腹部整形术术后疼痛最大程度相一致的术后镇痛效果，并具有良好的安全性。
NCT04785625。
