UCLA IPF Clinical Research Network

描述(由申请人提供)： 这项建议的总体目标是发现治疗特发性肺纤维化的新疗法。我们提出了两个项目。第一个项目旨在确定西罗莫司联合干扰素-1b治疗138例特发性肺纤维化(IPF)的安全性和有效性。我们提出了一项为期两年的多中心、随机、双盲、对照研究，将西罗莫司联合干扰素-γ1b与干扰素-γ1b+安慰剂用于特发性肺纤维化患者。符合条件的患者将被随机分配，比例为2：1，分别接受西罗莫司加干扰素-γ1b和干扰素-γ1b+安慰剂。随机化将使用随临床分层的随机化排列区块设计，并改变区块大小。主要疗效结果是6分钟步行距离(6MWD)。次级疗效终点包括肺功能、气体交换和生活质量(QOL)。我们假设轻中度IPF的患者(FVC&GT；55%和DLCO&GT；30%的预测值)将在联合治疗的96周内在6MWD表现出稳定或改善。预计对照组将表现出6MWD的恶化。 第二个项目旨在确定西地那非对100名患有IPF和中度肺动脉高压(PAH；定义为静息状态下的肺动脉压<30 mm Hg)患者的安全性和有效性。我们提出了一项为期12周的多中心、随机、双盲、对照研究，将西地那非与安慰剂在IPF和PAH患者中进行比较。符合条件的患者将被同等随机(1：1)分为试验组或安慰剂组。临床随机采用分层排列区组设计。主要的疗效结果是6MWD。次级疗效终点包括气体交换和生活质量(QOL)。我们预计，与接受安慰剂的患者相比，接受西地那非治疗的患者6MWD会有所改善。(摘要结束)

DESCRIPTION (provided by applicant): The overall objective of this proposal is to discover novel therapy for the treatment of IPF. We propose two projects. The first project aims to determine the safety and efficacy of sirolimus combined with interferon gamma-1b (IFN-y lb) in 138 patients with idiopathic pulmonary fibrosis (IPF). We propose a two-year multi-center, randomized, double-blinded, controlled study of sirolimus plus IFN-y lb compared to IFN-y lb plus placebo in patients with IPF. Eligible patients will be randomly assigned, in a 2:1 ratio, to receive sirolimus plus IFN-y lb versus IFN-y lb plus placebo, respectively. Randomization will use a randomized permuted block design stratified by clinic with changing block sizes. The primary efficacy outcome is the 6-minute walk distance (6MWD). Secondary efficacy endpoints include pulmonary function, gas exchange, and quality of life (QOL). We hypothesize that patients with mild to moderate IPF (FVC >55% and DLCO >30% of predicted) will demonstrate stabilization or improvement in 6MWD over 96 weeks of treatment with combined therapy. The control group will be expected to demonstrate deterioration in 6MWD. The second project aims to determine the safety and efficacy of sildenafil in 100 patients with IPF and moderate pulmonary arterial hypertension (PAH; defined as meaning pulmonary arterial pressure >30 mm Hg at rest). We propose a 12-week multi-center, randomized, double-blinded, controlled study of sildenafil compared placebo in patients with IPF and PAH. Eligible patients will be equally randomized (1:1) into active or placebo groups. Randomization will use the permuted block design with stratification by clinic. The primary efficacy outcome is the 6MWD. Secondary efficacy endpoints include gas exchange and quality of life (QOL). We anticipate an improvement in 6MWD in patients who receive sildenafil compared to those who receive placebo. (End of Abstract)