注射用羟丙基-β-环糊精-双氯芬酸在老年急性中重度术后疼痛患者中的安全性：三项III期试验的汇总分析

Safety of Injectable HPβCD-Diclofenac in Older Patients with Acute Moderate-to-Severe Postoperative Pain: A Pooled Analysis of Three Phase III Trials.

作者信息

Chelly Jacques E, Lacouture Peter G, Reyes Christian Russel D

机构信息

Division of Interventional Perioperative Pain, Department of Anesthesiology, University of Pittsburgh and University of Pittsburgh Medical Center, Aiken Medical Building, 532 S Aiken Avenue, Suite 407, Pittsburgh, PA, 15232, USA.

Magidom Discovery, LLC, St. Augustine, FL, 32080, USA.

出版信息

Drugs Aging. 2018 Mar;35(3):249-259. doi: 10.1007/s40266-018-0529-3.

DOI:10.1007/s40266-018-0529-3

PMID:29492863

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5884896/

Abstract

BACKGROUND

Hydroxypropyl-β-cyclodextrin-diclofenac (HPβCD-diclofenac) is an NSAID used to treat acute moderate-to-severe postoperative pain. This post hoc analysis investigated the safety of HPβCD-diclofenac in patients aged ≥ 65 years.

METHODS

Data from three phase III trials of HPβCD-diclofenac in adult patients with acute moderate-to-severe postoperative pain were pooled (NCT00448110, NCT00507026, and NCT00726388). Patients who received one or more dose of HPβCD-diclofenac or placebo were included and stratified according to age: < 65, 65-74, or ≥ 75 years. Numerical and categorical variables were compared across the groups using ANOVA and Cochran-Mantel-Haenszel tests, respectively. Cochran-Mantel-Haenszel relative risks compared with placebo were calculated, adjusted by study.

RESULTS

Overall, 1289 patients were included: 878, 282, and 129 in the < 65, 65-74, and ≥ 75-years groups, respectively. Overall incidence of treatment-emergent adverse events (TEAEs) was similar in the three groups (p = 0.4360). Incidences of postoperative anemia (p < 0.0001), constipation (p = 0.0017), and hypotension (p = 0.0003) increased significantly across the age groups, whereas headache (p = 0.0008) and flatulence (p = 0.0118) decreased significantly. Relative risks for all System Organ Class categories and preferred terms investigated were similar among the groups and similar to placebo.

CONCLUSIONS

Overall incidence of TEAEs in patients aged 65-74 or ≥ 75 years was similar to patients aged < 65 years. The groups displayed similar relative risks for the most frequent TEAEs, which were all similar to placebo. The TEAE profiles of the groups showed differences, all of which may be anticipated due to age-related differences in susceptibility and the types of surgery most commonly performed in each group. CLINICALTRIALS.

GOV IDENTIFIERS

NCT00448110, NCT00507026, and NCT00726388.

摘要

背景

羟丙基-β-环糊精-双氯芬酸（HPβCD-双氯芬酸）是一种用于治疗急性中度至重度术后疼痛的非甾体抗炎药。这项事后分析研究了HPβCD-双氯芬酸在≥65岁患者中的安全性。

方法

汇总了三项HPβCD-双氯芬酸治疗成年急性中度至重度术后疼痛患者的III期试验数据（NCT00448110、NCT00507026和NCT00726388）。纳入接受一剂或多剂HPβCD-双氯芬酸或安慰剂的患者，并根据年龄分层：<65岁、65 - 74岁或≥75岁。分别使用方差分析和 Cochr an-Mantel-Haenszel检验对各组的数值和分类变量进行比较。计算与安慰剂相比的 Cochr an-Mantel-Haenszel相对风险，并按研究进行调整。

结果

总体上，共纳入1289例患者：<65岁组878例、65 - 74岁组282例、≥75岁组129例。三组治疗中出现的不良事件（TEAE）总体发生率相似（p = 0.4360）。术后贫血（p < 0.0001）、便秘（p = 0.0017）和低血压（p = 0.0003）的发生率在各年龄组中显著增加，而头痛（p = 0.0008）和肠胃胀气（p = 0.0118）显著减少。所有系统器官分类类别和所研究的首选术语的相对风险在各组之间相似，且与安慰剂相似。