SCLERODERMA LUNG STUDY

硬皮病肺部研究

• 批准号: 2898415
• 负责人: REDA E GIRGIS
• 金额: $ 4.7万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-10 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2898415
• 关键词: clinical research; cooperative study; cyclophosphamide; diagnostic respiratory lavage; drug screening /evaluation; dyspneas; functional ability; human subject; human therapy evaluation; inflammation; longitudinal human study; lung alveolus; pulmonary fibrosis /granuloma; quality of life; respiratory airway volume; respiratory disorder chemotherapy; systemic scleroderma

In Systemic Sclerosis (SSc), interstitial pulmonary fibrosis is frequent (80%) and is now the leading cause of death. The mortality rate of patients with a forced vital capacity (FVC) <50% of predicted due to SSc pulmonary fibrosis is 40-45% within 10 years of SSc onset. Present evidence suggests that pulmonary fibrosis, which occurs early in the course of SSc, is usually preceded by inflammation which can be detected by examination of cells obtained by bronchoalveolar lavage (BAL). Uncontrolled series suggest that cyclophosphamide (CYC) may stabilize or improve lung function in SSc patients with active alveolitis. We propose to conduct a five- year, l3-center, parallel-group, double-blind, randomized controlled study of oral CYC (1-2 mg/kg/day) versus placebo to assess the efficacy of CYC in stabilizing or improving the course of FVC (as % predicted) in 163 patients with early SSc (within 5 years of clinical disease onset) who are already dyspneic (at least moderate functional impairment and perceived magnitude of task and effort on the Mahler Baseline Dyspnea Index), have an FVC equal to or <85% of predicted and exhibit active alveolitis defined as equal to or >3.0% neutrophils or equal to or >2.0% eosinophils in BAL fluid. Secondarily, we will assess the impact of CYC on quality of life (SF36), functional activity (SSc Health Assessment Questionnaire), dyspnea (Mahler Transition Dyspnea Index) and diffusing capacity for carbon monoxide (DLCO) in these patients. Patients will be recruited for study during the first 3 years (from 6 mos. to 2 yrs, 9 mos) of the 5-year project period. Randomized participants will be treated with study drug for 1 year and followed at 3-month intervals for 2 years. Overall study coordination and data collection, management and analysis will be centralized at UCLA. Proven methods for analyzing time-oriented data employed by the investigators in previous controlled studies of scleroderma will be used to evaluate whether oral CYC (1-2 mg/kg/day) is better than placebo a) in improving or preventing worsening of FVC (the primary outcome variable) and b) in improving or preventing worsening of quality of life, functional ability, breathlessness and DLCO (secondary outcome variables).

在系统性硬化症（SSc）中，间质性肺纤维化是常见的（80%），现在是死亡的主要原因。由于SSc肺纤维化，用力肺活量（FVC）<预测值50%的患者在SSc发作后10年内的死亡率为40-45%。目前的证据表明，肺纤维化，这发生在早期的SSc过程中，通常是由炎症，可以检测到的检查细胞获得支气管肺泡灌洗（BAL）。 非对照系列研究表明，环磷酰胺（CYC）可以稳定或改善活动性肺泡炎SSc患者的肺功能。我们建议进行一项为期5年的，13个中心，平行组，双盲，口服CYC的随机对照研究（1-2 mg/kg/天）与安慰剂比较，以评估CYC在稳定或改善FVC病程方面的疗效（%预测值）（临床疾病发作后5年内）已患有呼吸困难的患者（至少中度功能损害，并且根据Mahler基线呼吸困难指数感知任务和努力的程度），具有等于或<85% of predicted and exhibit active alveolitis defined as equal to or >3.0%中性粒细胞或等于或&gt;2.0%嗜酸性粒细胞的BAL液FVC。其次，我们将评估CYC对这些患者的生活质量（SF 36）、功能活动（SSc健康评估问卷）、呼吸困难（Mahler过渡期呼吸困难指数）和一氧化碳弥散量（DLCO）的影响。将在前3年（从6个月开始）招募患者参加研究。至2年9个月）。 随机化受试者将接受研究药物治疗1年，并每隔3个月随访2年。总体研究协调和数据收集、管理和分析将集中在UCLA。将使用研究者在先前硬皮病对照研究中采用的时间导向数据分析方法，评价口服CYC（1-2 mg/kg/天）是否优于安慰剂a）在改善或预防FVC恶化（主要结局变量）和B）在改善或预防生活质量、功能能力、呼吸困难和DLCO恶化（次要结局变量）方面。