A Prospective, Multicenter, Double-Blind, Randomized Trial of Bladder Instillation of Liposome Formulation OnabotulinumtoxinA for Interstitial Cystitis/Bladder Pain Syndrome
A Prospective, Multicenter, Double-Blind, Randomized Trial of Bladder Instillation of Liposome Formulation OnabotulinumtoxinA for Interstitial Cystitis/Bladder Pain Syndrome
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DOI：
10.1016/j.juro.2017.02.021
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发表时间：
2017-08-01
影响因子：
6.6
通讯作者：
Kuo, Hann-Chorng
中科院分区：
文献类型：
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作者：
Chuang, Yao-Chi;Kuo, Hann-Chorng
目的：膀胱内滴注脂质体配方的肉毒杆菌毒素 A（脂毒素）已显示出无需针头注射即可治疗难治性膀胱过度活动症的治疗效果。我们评估了脂毒素治疗难治性间质性膀胱炎/膀胱疼痛综合征的效果。 材料和方法：这项由医生发起的 2 中心、双盲、随机、安慰剂对照研究纳入了难治性间质性膀胱炎/膀胱疼痛综合征患者。总共 31 名患者被分配接受脂毒素（onabotulinumtoxinA 200 U 与 80 mg 鞘磷脂）膀胱内滴注，28 名患者被分配接受 200 U 的 onabotulinumtoxinA 生理盐水治疗，31 名患者被分配仅接受生理盐水治疗。主要终点是 O'Leary-Sant 症状评分的平均变化，包括基线和治疗后 4 周之间的 ICSI（间质性膀胱炎症状指数）和 ICPI（间质性膀胱炎问题指数）。其他终点包括 3 天排尿日记的平均变化、疼痛的视觉模拟量表以及患者满意度的整体反应评估。 结果：治疗 4 周后，所有 3 组的疼痛量表和 O'Leary-Sant 症状评分均出现改善。脂毒素滴注与 O'Leary-Sant 症状评分（平均值 +/- SD 7.38 +/- 8.75）、ICSI（4.00 +/- 4.28）、ICPI（3.35 +/- 5.11）和视觉模拟量表疼痛量表（1.64 +/- 2.52）显着下降以及总体反应评估（1.35 +/- 1.28）的增加相关。然而，三组之间的改善没有差异。在任何组中均未发现明显的不良事件。 结论：与肉毒杆菌毒素 A 或安慰剂相比，脂毒素未能表现出积极的概念证明。然而，与中度至重度间质性膀胱炎/膀胱疼痛综合征患者的基线相比，单次膀胱内滴注脂毒素与间质性膀胱炎/膀胱疼痛综合征症状减轻相关。这种效应可能是由于显着的安慰剂效应所致。
Purpose: Intravesical instillation of liposomal formulated botulinum toxin A (lipotoxin) has shown therapeutic effects as treatment of refractory overactive bladder without needle injections. We assessed lipotoxin to treat refractory interstitial cystitis/bladder pain syndrome.Materials and Methods: This 2-center, double-blind, randomized, placebo controlled, physician initiated study enrolled patients with refractory interstitial cystitis/bladder pain syndrome. A total of 31 patients were assigned to intravesical instillation of lipotoxin (onabotulinumtoxinA 200 U with 80 mg sphingomyelin), 28 were assigned to onabotulinumtoxinA 200 U in normal saline and 31 were assigned to normal saline alone. The primary end point was the average change in O'Leary-Sant symptom scores, including ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index) between baseline and 4 weeks after treatment. Other end points included the average changes in a 3-day voiding diary, a visual analog scale for pain and a global response assessment of patient satisfaction.Results: Improvements in the pain scale and O'Leary-Sant symptom scores occurred in all 3 groups by 4 weeks after treatment. Lipotoxin instillation was associated with a statistically significant decrease in O'Leary-Sant symptom scores (mean +/- SD 7.38 +/- 8.75), ICSI (4.00 +/- 4.28), ICPI (3.35 +/- 5.11) and the visual analog scale pain scale (1.64 +/- 2.52), and an increase in the global response assessment (1.35 +/- 1.28). However, there was no difference in improvement among the 3 groups. No significant adverse events were found in any group.Conclusions: Lipotoxin failed to demonstrate a positive proof of concept compared to onabotulinumtoxinA or placebo. However, a single intravesical instillation of lipotoxin was associated with decreased interstitial cystitis/bladder pain syndrome symptoms compared to baseline in patients with moderate to severe interstitial cystitis/bladder pain syndrome. The effect was likely due to a significant placebo effect.