Provencher Steeve, Paruchuru Patrap, Spezzi Andrea, Waterhouse Brian, Gomberg-Maitland Mardi
Pulmonary Hypertension Research Group, Centre de recherche de l'Institut Universitaire de cardiologie et de pneumologie de Québec, Université Laval, Québec, Québec, Canada.
GlaxoSmithKline R&D, 980 Great West Road, Brentford, United Kingdom.
PLoS One. 2015 Mar 20;10(3):e0120657. doi: 10.1371/journal.pone.0120657. eCollection 2015.
Flolan (epoprostenol sodium) is most commonly prescribed to patients with severe pulmonary arterial hypertension (PAH) owing to the requirement that the drug be delivered by continuous intravenous infusion and the reconstituted solution may only be administered up to 24 hours when it is maintained between a temperature of 2°C and 8°C. The aim of this single-arm, open label study was to describe the effects of the new thermostable formulation of Flolan on health-related quality of life (HRQoL) and ease of administration in subjects switching from the currently marketed Flolan to the reformulated product.
Following a 4-week run-in period and after 4 weeks of treatment with the reformulated product, patients completed the SF-36 HRQoL questionnaire and a study-specific questionnaire evaluating ease of administration, along with World Health Organization (WHO) functional class, six-minute walked distance (6MWD) and N-terminal-pro B-type natriuretic peptide (NT-proBNP) assessment.
16 participants completed the study. The SF-36 scores remained unchanged from baseline to Week 4. Conversely, there were small improvements for the majority of the study-specific questionnaire items and 14 (88%) subjects preferred the reformulated product to the currently marketed Flolan. There was no significant change in the dose of reformulated product, 6MWD, Borg dyspnoea index, WHO functional class and mean NT-proBNP levels. No significant changes in haemodynamic parameters were seen from baseline to 2 hours post transition in a subset of patients undergoing catheterization.
The reformulated product was not associated with significant improvement in HRQoL compared with the currently marketed Flolan as measured by the SF-36. However, most subjects preferred the reformulated product to the currently marketed Flolan. Moreover, the 2 formulations of Flolan had similar safety and efficacy profiles.
ClinicalTrials.gov NCT01462565.
由于需要通过持续静脉输注给药，且重构后的溶液在2°C至8°C之间保存时仅可在24小时内使用，因此弗洛兰（依前列醇钠）最常用于重度肺动脉高压（PAH）患者。这项单臂、开放标签研究的目的是描述新型热稳定剂型的弗洛兰对从当前市售弗洛兰转换为重新配方产品的受试者的健康相关生活质量（HRQoL）和给药便利性的影响。
在为期4周的导入期后，以及在用重新配方产品治疗4周后，患者完成了SF-36 HRQoL问卷和一份评估给药便利性的特定研究问卷，同时进行了世界卫生组织（WHO）功能分级、六分钟步行距离（6MWD）和N末端B型利钠肽原（NT-proBNP）评估。
16名参与者完成了研究。从基线到第4周，SF-36评分保持不变。相反，大多数特定研究问卷项目有小幅改善，14名（88%）受试者更喜欢重新配方的产品而非当前市售的弗洛兰。重新配方产品的剂量、6MWD、博格呼吸困难指数、WHO功能分级和平均NT-proBNP水平没有显著变化。在接受导管插入术的一部分患者中，从基线到转换后2小时，血流动力学参数没有显著变化。
与当前市售的弗洛兰相比，通过SF-36测量，重新配方的产品在HRQoL方面没有显著改善。然而，大多数受试者更喜欢重新配方的产品而非当前市售的弗洛兰。此外，两种弗洛兰制剂具有相似的安全性和疗效。
ClinicalTrials.gov NCT01462565。
