Hill Nicholas S, Feldman Jeremy P, Sahay Sandeep, Benza Raymond L, Preston Ioana R, Badesch David, Frantz Robert P, Patel Savan, Galloway Ashley, Bull Todd M
Tufts Medical Center Boston Massachusetts USA.
Arizona Pulmonary Specialists, Ltd Phoenix Arizona USA.
Pulm Circ. 2022 Jul 1;12(3):e12119. doi: 10.1002/pul2.12119. eCollection 2022 Jul.
The INSPIRE trial was a Phase 3, open-label, multicenter trial (LTI-301) that enrolled patients with pulmonary arterial hypertension (PAH) ≥ 18 years of age who transitioned to Yutrepia from nebulized treprostinil (Transition) or added Yutrepia to prostacyclin naïve patients on ≤2 nonprostacyclin oral therapies. The objectives of the trial were to evaluate the safety and tolerability of Yutrepia (dry-powder formulation of treprostinil) in patients with PAH. The primary safety measures were the incidence of adverse events (AEs) and serious AEs. Exploratory efficacy measures were also assessed during the trial. Transition patients initiated Yutrepia at a dose comparable to their nebulized treprostinil dose while prostacyclin naïve patients received 26.5-mcg QID; up-titration in 26.5-mcg increments was permitted for both groups. A total of 121 patients were enrolled, of which 29 patients discontinued from the trial, with the most common reason being AEs. Eighty percent of the Transition group and 96% of the prostacyclin naïve group titrated to a dose ≥79.5 mcg QID at Day 360, respectively, with one patient achieving a dose of 212-mcg QID. The most common AEs were cough, headache, upper respiratory tract infection, dyspnea, dizziness, throat irritation, diarrhea, chest discomfort, fatigue, and nasopharyngitis. Most of these events were considered treatment-related though mild to moderate in severity and expected for prostacyclin therapy administered by inhalation. In an evaluation of exploratory efficacy measures, patients remained stable or improved over the 1 year of treatment. Yutrepia was found to be a convenient, safe, and well-tolerated inhaled prostacyclin treatment option for PAH patients.
INSPIRE试验是一项3期、开放标签、多中心试验（LTI-301），纳入年龄≥18岁、从雾化曲前列尼尔转换为优拓比（Yutrepia）（转换组）或在接受≤2种非前列环素口服治疗的初治前列环素患者中加用优拓比的肺动脉高压（PAH）患者。该试验的目的是评估优拓比（曲前列尼尔干粉制剂）在PAH患者中的安全性和耐受性。主要安全性指标为不良事件（AE）和严重AE的发生率。试验期间还评估了探索性疗效指标。转换组患者起始使用优拓比的剂量与其雾化曲前列尼尔剂量相当，而初治前列环素患者接受26.5 mcg每日4次的剂量；两组均允许以26.5 mcg的增量进行滴定。共纳入121例患者，其中29例患者退出试验，最常见的原因是AE。转换组80%的患者和初治前列环素组96%的患者在第360天时滴定至≥79.5 mcg每日4次的剂量，1例患者达到212 mcg每日4次的剂量。最常见的AE为咳嗽、头痛、上呼吸道感染、呼吸困难、头晕、咽喉刺激、腹泻、胸部不适、疲劳和鼻咽炎。这些事件大多被认为与治疗相关，尽管严重程度为轻至中度，且吸入前列环素治疗时可预期。在探索性疗效指标评估中，患者在1年的治疗期间保持稳定或有所改善。优拓比被发现是一种方便、安全且耐受性良好的PAH患者吸入性前列环素治疗选择。
