Efficacy of fentanyl buccal tablet and morphine for exertional dyspnoea in patients with cancer: a double-blind, placebo-controlled, randomised clinical trial.

Previous single-dose studies found that prophylactic administration of fentanyl buccal tablet (FBT) improved exertional dyspnoea.

先前的单剂量研究发现，预防性使用芬太尼颊膜片（FBT）可以改善劳力性呼吸困难。

In this randomised trial, we compared daily use of prophylactic FBT, oral morphine and placebo on exertional dyspnoea over 14 days.

在这项随机试验中，我们比较了预防性FBT、口服吗啡和安慰剂在14天内对劳力性呼吸困难的影响。

Methods

This parallel, double-blind, randomised clinical trial enrolled opioid-tolerant patients with cancer and exertional dyspnoea.

这项平行、双盲、随机临床试验招募了对阿片类药物耐受的癌症患者和劳力性呼吸困难患者。

After a 5-day observation period, patients were randomised (1:1:1) to receive FBT, morphine or placebo 30 min before daily structured activity for 14 days.

经过5天的观察期后，患者被随机分配（1:1:1）在每日结构化活动前30分钟接受FBT、吗啡或安慰剂治疗，持续14天。

Shuttle walk tests (SWTs) were conducted on days 1/5/8/12/15/19.

在第1/5/8/12/15/19天进行了穿梭行走测试（SWTs）。

The primary outcome was change in modified Borg Scale dyspnoea intensity during SWTs from day 5 to day 19, analysed using a mixed effects model with treatment, time and treatment×time interaction.

主要结果是从第5天到第19天的步行测试（SWTs）期间，通过混合效应模型分析改良Borg量表呼吸困难强度的变化，模型中考虑了治疗、时间和治疗与时间的交互作用。

SWT distance was a key secondary outcome.

步行测试（SWT）距离是关键的次要结果。

Results

67 patients were enrolled and 56 (84%) were randomised.

共有67名患者参与研究，其中56名（占84%）被随机分配。

Over the 14-day blinded phase, we observed a significant decrease in the magnitude of dyspnoea intensity change during the SWTs in all three groups, with no significant difference by treatment group (slope change from day 5 to day 19: FBT -2.2 (95% CI -2.9 to -1.6); morphine -1.9 (95% CI -2.7 to -1.2); placebo -2.2 (95% CI -3 to -1.4); time effect p<0.001, treatment×time effect p=0.79).

在14天的双盲阶段，我们观察到所有三组患者在SWTs期间呼吸困难强度变化的幅度显著减少，且按治疗组分组后没有显著差异（从第5天到第19天的变化斜率：FBT -2.2（95%置信区间-2.9至-1.6）；吗啡-1.9（95%置信区间-2.7至-1.2）；安慰剂-2.2（95%置信区间-3至-1.4）；时间效应p<0.001，治疗×时间效应p=0.79）。

SWT distance increased significantly over time (FBT +93 m; morphine +84 m; placebo +76 m) but did not differ by treatment (p=0.71).

SWT距离随时间显著增加（FBT+93米；吗啡+84米；安慰剂+76米），但治疗间无差异（p=0.71）。

Few adverse events were reported.

报告的不良事件很少。

Conclusions

All three groups reported less dyspnoea while walking farther; however, no difference was detected between opioids and placebo.

所有三组报告在行走更远时呼吸困难减轻；然而，在阿片类药物和安慰剂之间未检测到差异。

These findings should be considered preliminary given the underpowered sample.

鉴于样本量不足，这些发现应被视为初步结果。

trial_registration_number

NCT04188418.

NCT04188418。