芬太尼吸入剂治疗爆发性癌痛的疗效和安全性：一项多中心、随机、双盲、安慰剂对照试验。
Efficacy and safety of fentanyl inhalant for the treatment of breakthrough cancer pain: a multicenter, randomized, double-blind, placebo-controlled trial.
机构信息
Department of Abdominal Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian, China.
First Hospital of Jiaxing, Jiaxing, Zhejiang, China.
出版信息
BMC Palliat Care. 2024 Sep 7;23(1):222. doi: 10.1186/s12904-024-01554-9.
BACKGROUND
Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25μg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients.
METHODS
The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30).
RESULTS
A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs.
CONCLUSION
Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.
背景
突破性癌痛（BTcP）对患者的生活质量、日常活动有负面影响，且与更差的临床结局相关。芬太尼吸入剂是一种手持组合药物-器械输送系统，通过加热产生的气溶胶吸入，可实现快速、多剂量（25μg/剂）给予芬太尼。这项多中心、随机、安慰剂对照、多次交叉、双盲研究评估了芬太尼吸入剂治疗阿片类药物耐受的癌症患者 BTcP 的疗效、安全性和耐受性。
方法
该试验纳入了每日有 1 至 4 次 BTcP 发作的阿片类药物耐受的癌症患者。每位患者接受治疗并观察 6 次 BTcP 发作（4 次给予芬太尼吸入剂，2 次给予安慰剂）。在每次 BTcP 发作中，患者允许最多吸入 6 次，两次剂量之间至少间隔 4 分钟。主要结局为 30 分钟时 PID（疼痛强度差）评分的时间加权总和（SPID30）。
结果
59 例患者共治疗了 335 次 BTcP 发作。芬太尼吸入剂治疗的发作的平均 SPID30 为-97.4±48.43，安慰剂治疗的发作的平均 SPID30 为-64.6±40.25（p<0.001）。芬太尼吸入剂与安慰剂治疗的发作的 PID 差异早在 4 分钟时就有显著差异，并持续至 60 分钟。30 分钟时报告 PI（疼痛强度）评分≤3、PI 评分降低≥33%或≥50%、PR30（30 分钟疼痛缓解评分）和 SPID60 的发作比例均有利于芬太尼吸入剂优于安慰剂。芬太尼吸入剂组仅 4.4%的 BTcP 发作需要使用解救药物。大多数不良事件为轻度或中度严重程度，与阿片类药物的典型不良事件一致。
结论
芬太尼吸入剂治疗 BTcP 具有显著的镇痛效果，且在给药后很快起效，是一种有前途的治疗选择。需要更大规模的 III 期试验来证实其有效性。
试验注册
ClinicalTrials.gov：NCT05531422 于 2022 年 9 月 6 日在主要修订后注册，NCT04713189 于 2021 年 1 月 14 日注册。
Zotero 插件