ORAL CYCLOPHOSPHAMIDE VS ORAL PLACEBO IN SSC ALVEOLITIS

口服环磷酰胺与口服安慰剂治疗 SSC 肺泡炎

• 批准号: 6184780
• 负责人: Kevin K Brown
• 金额: $ 10.21万
• 依托单位: NATIONAL JEWISH HEALTH
• 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 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6184780
• 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，间质肺纤维化经常（80％），现在是死亡的主要原因。在SSC发作后的10年内，由于SSC肺纤维化而导致的强迫生命力（FVC）<50％的患者的死亡率<50％。目前的证据表明，在SSC过程中发生的肺纤维化通常是在炎症之前发生的，可以通过检查通过支气管肺泡灌洗（BAL）检测细胞来检测。 不受控制的序列表明，环磷酰胺（CYC）可能在活性肺泡炎的SSC患者中稳定或改善肺功能。我们建议对口服CYC（1-2 mg/kg/kg/day）进行五年的L3中心，平行组，双盲，随机对照研究，以评估CYC在163例早期SSC（至少在临床疾病上）（至少在临床疾病上的5年代）中，CYC在稳定或改善FVC方案（AS％预测）中的疗效（至少是临床疾病）的疗效。在Mahler基线呼吸困难指数上的任务和努力的幅度幅度，其FVC等于预测的预测肺泡炎和<85％的活性肺泡炎，其定义为等于或> 3.0％的中性粒细胞或等于或等于或等于或等于或等于或> 2.0％的BAL流体嗜酸脂蛋白。其次，我们将评估CYC对生活质量（SF36），功能活性（SSC健康评估问卷），呼吸困难（Mahler过渡呼吸困难指数）和碳一氧化碳（DLCO）的影响。在5年项目期间的头三年（从6个月至2年）中，将招募患者进行研究。 随机参与者将用研究药物治疗1年，并以3个月的间隔进行2年。总体研究协调和数据收集，管理和分析将集中在UCLA。研究人员在先前对硬皮病的对照研究中采用的分析时间导向数据的可行方法将用于评估口服CYC（1-2 mg/kg/day）是否比安慰剂a更好地改善或预防FVC（主要结果变量）和b）在改善或防止质量和b）的情况下改善或预防效果的差异或预防效果，又有质量和b）的效果，又有多种多样的能力。变量）。