Vocacapsaicin 用于术后疼痛管理的安全性和疗效：一项随机临床试验。

Safety and Efficacy of Vocacapsaicin for Management of Postsurgical Pain: A Randomized Clinical Trial.

机构信息

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California.

Clinical Development, Concentric Analgesics, Inc., San Francisco, California.

出版信息

Anesthesiology. 2024 Aug 1;141(2):250-261. doi: 10.1097/ALN.0000000000005027.

DOI:10.1097/ALN.0000000000005027

PMID:38662910

Abstract

BACKGROUND

Nonopioid management of postsurgical pain remains a major unmet need. Few studies have evaluated transient receptor potential vanilloid subfamily member 1 agonists for analgesia after surgery. This study examines intraoperative vocacapsaicin, a novel prodrug of the transient receptor potential vanilloid subfamily member 1 agonist capsaicin, in a validated model of postsurgical pain.

METHODS

This was a triple-blinded, randomized, placebo-controlled, dose-ranging trial in patients undergoing bunionectomy. Patients were randomized 1:1:1:1 to surgical site administration of 14 ml of placebo or one of three vocacapsaicin concentrations: 0.30, 0.15, or 0.05 mg/ml. The prespecified primary endpoint was the area-under-the-curve of the numerical rating scale pain score at rest through 96 h for the 0.30 mg/ml group. Prespecified ordered, secondary endpoints for the 0.30 mg/ml group included the percentage of patients who did not require opioids from 0 to 96 h, total opioid consumption through 96 h, and the area-under-the-curve of the numerical rating scale pain score for the first week.

RESULTS

The 147 patients were randomized. During the first 96 h, vocacapsaicin (0.30 mg/ml) reduced pain at rest by 33% versus placebo (primary endpoint, 95% CI [10%, 52%], effect size [Cohen's d] = 0.61, P = 0.005). Of patients receiving vocacapsaicin (0.30 mg/ml), 26% did not require postoperative opioids for analgesia (P = 0.025) versus 5% of patients receiving placebo. Vocacapsaicin (0.30 mg/ml) reduced opioid consumption over the first 96 h by 50% versus placebo (95% CI [26%, 67%], effect size = 0.76, P = 0.002). Vocacapsaicin (0.30 mg/ml) reduced pain over the first week by 37% versus placebo (95% CI [12%, 57%], effect size = 0.62, P = 0.004). The treatment effect persisted for at least 2 weeks. All study endpoints showed an administered concentration-versus-response relationship. Vocacapsaicin was well tolerated with no differences between groups in any safety parameter.

CONCLUSIONS

A single, local administration of vocacapsaicin during surgery reduced pain and opioid consumption for at least 96 h after surgery compared to control.

摘要

背景

非阿片类药物管理术后疼痛仍然是一个主要的未满足的需求。很少有研究评估过瞬时受体电位香草素亚家族成员 1 激动剂在手术后的镇痛作用。本研究在术后疼痛的验证模型中评估了术中 vocacapsaicin，一种瞬时受体电位香草素亚家族成员 1 激动剂辣椒素的新型前药。

方法

这是一项在接受拇囊炎切除术的患者中进行的三盲、随机、安慰剂对照、剂量范围试验。患者以 1:1:1:1 的比例随机分配至手术部位给予 14ml 安慰剂或三种 vocacapsaicin 浓度之一：0.30、0.15 或 0.05mg/ml。主要终点是 0.30mg/ml 组在休息时数字评分量表疼痛评分的曲线下面积在 96 小时内的情况。0.30mg/ml 组的预设有序次要终点包括从 0 到 96 小时不需要阿片类药物的患者百分比、96 小时内的阿片类药物总消耗量以及第一周数字评分量表疼痛评分的曲线下面积。

结果

147 名患者被随机分配。在最初的 96 小时内， vocacapsaicin（0.30mg/ml）与安慰剂相比，在休息时减轻疼痛 33%（主要终点，95%CI[10%，52%]，效应大小[Cohen's d] = 0.61，P=0.005）。接受 vocacapsaicin（0.30mg/ml）治疗的患者中有 26%不需要术后阿片类药物镇痛（P=0.025），而接受安慰剂治疗的患者中有 5%。与安慰剂相比， vocacapsaicin（0.30mg/ml）在最初的 96 小时内减少了 50%的阿片类药物消耗（95%CI[26%，67%]，效应大小=0.76，P=0.002）。与安慰剂相比， vocacapsaicin（0.30mg/ml）在第一周内减轻疼痛 37%（95%CI[12%，57%]，效应大小=0.62，P=0.004）。治疗效果至少持续 2 周。所有研究终点均显示出浓度与反应之间的关系。 vocacapsaicin 耐受性良好，各组在任何安全性参数上均无差异。