Nathan Steven D, Lacasse Victoria, Bell Heidi, Sista Prakash, Di Marino Michael, Bull Todd, Tapson Victor, Waxman Aaron
Inova Fairfax Hospital Falls Church Virginia USA.
United Therapeutics Silver Spring Maryland USA.
Pulm Circ. 2024 Oct 2;14(4):e12430. doi: 10.1002/pul2.12430. eCollection 2024 Oct.
The PERFECT study, a randomized, controlled, double-blind study of inhaled treprostinil in patients with COPD and associated pulmonary hypertension (PH-COPD) was a negative trial that was terminated early. The reason(s) for the negative outcome remains uncertain. A post hoc analysis of data from the PERFECT study was undertaken to identify adverse responders and possibly potential responders. The goal was also to provide insight into phenotypes for possible inclusion and exclusion in future PH-COPD clinical trials. An adverse response on active treatment was seen in 36.4% (24/66) of the subjects compared to 27.6% (16/58) on placebo. There was no evidence to suggest that hyperinflation, bronchospasm, or occult heart failure played any role in the untoward outcomes of the study. The patients who died during the study all had baseline diffusing capacity for carbon monoxide ≤25% of predicted. Evidence of a potential response was seen in 10.6% (7/66) of the patients who received inhaled treprostinil. Patients who had evidence of a treatment response had a baseline mean pulmonary artery pressure of ≥40 mmHg and a forced expiratory volume in the first second of ≥40%. Change in N-terminal prohormone of brain natriuretic peptide did not predict clinical response. This post hoc analysis provides information that may potentially enable improved selection of patients for future therapeutic trials in PH-COPD. These analyses are post hoc, observational, and exploratory. The thresholds defining the spectrum of responders are preliminary and may require further refinement and validation in future studies.
PERFECT研究是一项针对慢性阻塞性肺疾病（COPD）合并肺动脉高压（PH-COPD）患者吸入曲前列尼尔的随机、对照、双盲研究，该研究结果为阴性且提前终止。阴性结果的原因尚不确定。对PERFECT研究的数据进行了事后分析，以识别不良反应者和可能的潜在反应者。其目的还在于深入了解可能纳入和排除在未来PH-COPD临床试验中的表型。与接受安慰剂治疗的27.6%（16/58）受试者相比，接受活性治疗的受试者中有36.4%（24/66）出现不良反应。没有证据表明肺过度充气、支气管痉挛或隐匿性心力衰竭在该研究的不良结局中起任何作用。在研究期间死亡的患者，其基线一氧化碳弥散能力均≤预测值的25%。在接受吸入曲前列尼尔治疗的患者中，有10.6%（7/66）出现潜在反应的证据。有治疗反应证据的患者，其基线平均肺动脉压≥40 mmHg，第一秒用力呼气量≥40%。脑钠肽前体N末端的变化并不能预测临床反应。这项事后分析提供的信息可能有助于在未来PH-COPD治疗试验中更好地选择患者。这些分析是事后的、观察性的和探索性的。定义反应者范围的阈值是初步的，可能需要在未来研究中进一步完善和验证。
