新型更耐热福莫特罗（前列环素）制剂在日本肺动脉高压（PAH）患者中的安全性和疗效研究 - 一项开放标签、单臂研究。
Investigation of safety and efficacy of the new more thermostable formulation of Flolan (epoprostenol) in Japanese patients with pulmonary arterial hypertension (PAH)-An open-label, single-arm study.
机构信息
Medicines Development, GlaxoSmithKline K.K., Tokyo, Japan.
Department of Clinical Science, National Hospital Organization Okayama Medical Center, Okayama, Japan.
出版信息
PLoS One. 2018 Apr 2;13(4):e0195195. doi: 10.1371/journal.pone.0195195. eCollection 2018.
OBJECTIVE
This study was conducted to evaluate the safety and efficacy of a new more thermostable Flolan (epoprostenol) solution prepared with the reformulated pH 12.0 diluent in Japanese patients with pulmonary arterial hypertension (PAH) receiving higher doses of Flolan than those typically administered in Western countries.
METHODS
This open-label, single-arm study was conducted in 10 Japanese PAH patients. During the run-in period, patients were intravenously infused with Flolan (45 ng/kg/min or higher doses) solution prepared with the existing pH 10.5 diluent. The patients were then switched to a new more thermostable Flolan solution prepared with the reformulated pH 12.0 diluent and observed for a 4-week treatment period. As a primary endpoint, safety after switching to the new Flolan solution was evaluated. Secondary endpoints included hemodynamics and the necessity for dose adjustment of Flolan in these patients.
RESULTS
All 10 patients completed the study period. Observed adverse events were nausea and hepatic function abnormal in 1 patient each, and both events were mild. No patients required dose adjustment due to the change from baseline in mean pulmonary artery pressure (mPAP) measured 3 hrs after switching to Flolan solution prepared with the reformulated diluent. No major changes from baseline in mPAP, pulmonary vascular resistance, or right atrial pressure were observed at 24 hrs and at 4 weeks after switching to the Flolan solution prepared with pH 12.0 diluent. Although some patients showed increases in cardiac output (CO) from baseline at 24 hrs and 4 weeks, no patients required dose reduction as a result of an increase in CO.
CONCLUSION
Neither safety/efficacy concerns nor any dose adjustments of Flolan after switching to a more thermostable Flolan solution prepared with the reformulated pH 12.0 diluent could be required in Japanese patients with PAH receiving higher doses of Flolan.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02705807.
目的
本研究旨在评估在接受高于西方国家常规剂量的前列环素（依前列醇）治疗的日本肺动脉高压（PAH）患者中，使用新配方 pH 值 12.0 稀释剂制备的更热稳定的 Flolan（依前列醇）溶液的安全性和疗效。
方法
这是一项开放标签、单臂研究，共纳入 10 例日本 PAH 患者。在导入期，患者接受现有 pH 值 10.5 稀释剂配制的 Flolan（45ng/kg/min 或更高剂量）溶液静脉输注。然后，患者转换为使用新配方 pH 值 12.0 稀释剂配制的更热稳定的 Flolan 溶液，并观察 4 周的治疗期。主要终点为转换为新 Flolan 溶液后的安全性。次要终点包括这些患者的血流动力学和 Flolan 剂量调整的必要性。
结果
所有 10 例患者均完成了研究期。观察到的不良事件为 1 例患者出现恶心和肝功能异常，均为轻度。由于从基线开始测量的 3 小时后切换到新 Flolan 溶液时平均肺动脉压（mPAP）的变化，没有患者需要调整剂量。在转换到新的 pH 值 12.0 稀释剂配制的 Flolan 溶液后 24 小时和 4 周时，mPAP、肺血管阻力或右心房压均无明显基线变化。尽管一些患者在 24 小时和 4 周时心输出量（CO）较基线增加，但由于 CO 增加，没有患者需要减少剂量。
结论
在接受更高剂量 Flolan 治疗的日本 PAH 患者中，转换为使用新配方 pH 值 12.0 稀释剂制备的更热稳定的 Flolan 溶液后，既不需要关注安全性/疗效问题，也不需要调整 Flolan 的剂量。
试验注册
ClinicalTrials.gov 标识符：NCT02705807。
Zotero 插件