STRIVE-IPF 试验设计——特发性肺纤维化急性加重症治疗性血浆置换、利妥昔单抗和静脉注射免疫球蛋白的研究。
Design of the STRIVE-IPF trial- study of therapeutic plasma exchange, rituximab, and intravenous immunoglobulin for acute exacerbations of idiopathic pulmonary fibrosis.
机构信息
Department of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, 1900 University Blvd. Tinsley Harrison Tower, Suite 422, Birmingham, AL, 35294, USA.
Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, USA.
出版信息
BMC Pulm Med. 2024 Mar 20;24(1):143. doi: 10.1186/s12890-024-02957-3.
BACKGROUND
Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.
METHODS
The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population with AE-IPF, as defined by American Thoracic Society criteria, while excluding patients with an alternative cause for a respiratory decompensation. The primary endpoint of this trial is six-month survival. Secondary endpoints include supplement oxygen requirement and six-minute walk distance which will be assessed immediately prior to treatment and after completion of therapy on day 19, as well as at periodic subsequent visits.
DISCUSSION
The experimental AE-IPF therapy proposed in this clinical trial was adapted from treatment regimens used in other antibody-mediated diseases. The regimen is initiated with TPE, which is expected to rapidly reduce circulating autoantibodies, followed by rituximab to reduce B-cells and finally IVIG, which likely has multiple effects, including affecting feedback inhibition of residual B-cells by Fc receptor occupancy. We have reported potential benefits of this experimental therapy for AE-IPF in previous anecdotal reports. This clinical trial has the potential to profoundly affect current paradigms and treatment approaches to patients with AE-IPF.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03286556.
背景
特发性肺纤维化（IPF）的急性加重（AE-IPF）影响了很大一部分 IPF 患者。尽管 AE-IPF 死亡率很高，但针对其治疗策略的数据却很有限。我们讨论了 STRIVE-IPF 的原理和设计，这是一项随机、多中心、开放标签的 IIb 期临床试验，旨在确定联合治疗性血浆置换（TPE）、利妥昔单抗和静脉注射免疫球蛋白（IVIG）与常规治疗（TAU）相比，在急性 IPF 加重患者中的疗效。
方法
STRIVE-IPF 试验将在美国五个地点随机分配 51 名患者。纳入标准旨在选择符合美国胸科学会标准的 AE-IPF 研究人群，同时排除因其他原因导致呼吸功能失代偿的患者。该试验的主要终点是六个月的生存率。次要终点包括补充氧气需求和六分钟步行距离，这些将在治疗前以及治疗第 19 天结束时进行评估，并在随后的定期就诊时进行评估。
讨论
本临床试验中提出的实验性 AE-IPF 治疗方案是从其他抗体介导疾病的治疗方案中改编而来的。该方案首先采用 TPE，预计可迅速降低循环自身抗体，然后采用利妥昔单抗减少 B 细胞，最后采用 IVIG，这可能具有多种作用，包括通过 Fc 受体占据影响残留 B 细胞的反馈抑制。我们之前在一些个案报告中报告了这种实验性治疗对 AE-IPF 的潜在益处。这项临床试验有可能深刻影响当前针对 AE-IPF 患者的治疗模式和方法。
试验注册
ClinicalTrials.gov 标识符：NCT03286556。
Zotero 插件