研究方案：探讨环磷酰胺联合皮质类固醇治疗特发性肺纤维化急性加重的疗效：一项随机、双盲、安慰剂对照、多中心 III 期试验（EXAFIP）。
Study protocol: exploring the efficacy of cyclophosphamide added to corticosteroids for treating acute exacerbation of idiopathic pulmonary fibrosis; a randomized double-blind, placebo-controlled, multi-center phase III trial (EXAFIP).
机构信息
Assistance Publique - Hôpitaux de Paris (AP-HP), Hôpital Tenon, Service de pneumologie, Site constitutif du centre de référence des maladies pulmonaires rares OrphaLung, Paris, France.
Unité de recherche clinique de l'est parisien (URCEst-CRCEst-CRB), Hôpital S Antoine, Hôpitaux Universitaires Paris Est (GH HUEP), Assistance Publique - Hôpitaux de Paris (AP-HP), Paris, France.
出版信息
BMC Pulm Med. 2019 Apr 11;19(1):75. doi: 10.1186/s12890-019-0830-x.
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease, with a median survival of 2-3 years and variable natural history, characterized by gradual and progressive deterioration. Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a severe complication, associated with poor survival and a mortality > 50%. To date, no treatment has proven effective in AE-IPF, with cyclophosphamide (CYC) the only therapy suggested to be effective on survival, primarily based on retrospective series. Considering the high fatality rates of AE-IPF, evaluating the efficacy of immunosuppressive agents in a randomized controlled trial proves crucial, as the results could significantly impact treatment and prognosis of AE-IPF.
METHODS
The EXAFIP study is a French national multicenter double-blind placebo-controlled randomized trial. Its primary objective is to evaluate the efficacy of CYC compared to placebo on early survival in patients treated with corticosteroids. We hypothesize that adding CYC to high-dose corticosteroids would reduce 3-month mortality in AE-IPF patients. The primary outcome is all-cause mortality rate at Month 3; secondary objectives are to evaluate the efficacy of CYC compared to placebo on overall survival at Months 6 and 12, respiratory disease-specific mortality, respiratory morbidity, and chest high-resolution computed tomography features, and to determine prognostic factors in AE-IPF and compare the safety of the two treatment arms during 6 months' follow-up.
DISCUSSION
There is an urgent unmet clinical need for effective AE-IPF treatment. The EXAFIP study is the first large Phase III placebo-controlled randomized trial evaluating the efficacy and safety of CYC added to corticosteroids in treating AE-IPF. The results of this study could significantly impact treatment strategy and prognosis of AE-IPF.
TRIAL REGISTRATION
Clinical trials, NCT02460588 ; Date: June 2, 2015, prospectively; Issue date: 14/11/2017; Protocole Amendment Number: 03.
背景
特发性肺纤维化（IPF）是一种致命的肺部疾病，中位生存期为 2-3 年，自然病程多变，表现为逐渐进行性恶化。特发性肺纤维化急性加重（AE-IPF）是一种严重的并发症，与生存不良和死亡率>50%相关。迄今为止，尚无治疗方法被证明对 AE-IPF 有效，环磷酰胺（CYC）是唯一被认为对生存有效的治疗方法，主要基于回顾性系列研究。鉴于 AE-IPF 的高死亡率，在随机对照试验中评估免疫抑制剂的疗效至关重要，因为结果可能会对 AE-IPF 的治疗和预后产生重大影响。
方法
EXAFIP 研究是一项法国全国多中心双盲安慰剂对照随机试验。其主要目的是评估 CYC 与安慰剂相比在接受皮质类固醇治疗的患者中的早期生存疗效。我们假设在 AE-IPF 患者中，将 CYC 加用至大剂量皮质类固醇可降低 3 个月时的死亡率。主要结局为 3 个月时的全因死亡率；次要结局为评估 CYC 与安慰剂相比在 6 个月和 12 个月时的总生存疗效、呼吸疾病特异性死亡率、呼吸发病率以及胸部高分辨率计算机断层扫描特征，并确定 AE-IPF 的预后因素，以及比较治疗组在 6 个月随访期间的安全性。
讨论
AE-IPF 的有效治疗存在迫切的临床需求。EXAFIP 研究是首个评估 CYC 加用皮质类固醇治疗 AE-IPF 的大型 III 期安慰剂对照随机试验。该研究的结果可能会显著影响 AE-IPF 的治疗策略和预后。
试验注册
临床试验，NCT02460588；日期：2015 年 6 月 2 日，前瞻性；发布日期：2017 年 11 月 14 日；方案修正案编号：03。
Zotero 插件