Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 202
- 试验地点
- 25
- 主要终点
- Time to one of the following composite endpoint criteria: 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplant or death from any cause.
研究概览
简要总结
The purpose of this study is to compare the effect of n-acetylcysteine (NAC) plus standard care with matched placebo plus standard of care in patients diagnosed with idiopathic pulmonary fibrosis (IPF) who have the TOLLIP rs3750920 TT genotype. The study will compare the time to a composite endpoint of relative decline in lung function [10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplantation, or all-cause mortality]
The secondary objectives will be to examine the effect of NAC on the components of the primary composite endpoint, the rates of clinical events, change in physiology, change in health status, and change in respiratory symptoms.
详细描述
This is a multi-center, randomized, double-blind, placebo-controlled trial of NAC or placebo in about 200 participants with IPF with a TOLLIP rs3750920 TT genotype.
Eligible participants will be randomized in a 1:1 fashion to NAC or placebo, stratified by stable concomitant IPF therapy use (i.e., pirfenidone or nintedanib administered for at least 6 weeks prior to screening) versus no pirfenidone or nintedanib use. Participants will receive 600 mg NAC orally or matched placebo to take three times daily for 24 months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The participant and site personnel will not know which study treatment the participant is receiving.
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥ 40 years of age
- •Diagnosed with IPF according to 2018 ATS/ERS/JRS/ALAT, confirmed by enrolling investigator
- •Signed informed consent
- •If taking pirfenidone or nintedanib, must be on stable dose for at least 6 weeks prior to enrollment visit
- •Confirmed rs3570920 TT TOLLIP genotype
排除标准
- •Pregnancy or planning to become pregnant
- •Women of childbearing potential not willing to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of <1% per year during study participation
- •Significant medical, surgical or psychiatric illness that in the opinion of the investigator would affect subject safety, including liver and renal failure
- •Receipt of an investigational drug or biological agent within the previous 4 weeks of the screening visit or 5 times the half-life, if longer
- •Supplemental or prescribed NAC therapy within 60 days of enrollment
- •Listed for lung transplantation at the time of screening
- •History of lung cancer
- •Inability to perform spirometry
- •Forced vital capacity (FVC) less than 45% predicted, using the global lung function index (GLI) equation at Visit 1
- •Active respiratory infection requiring treatment with antibiotics within 4 weeks of Visit 1
研究组 & 干预措施
Placebo
Placebo tablet three times daily for 24 months.
干预措施: Placebo (Drug)
N-acetylcysteine
600 mg oral N-acetylcysteine (NAC) three times daily for 24 months.
干预措施: N-acetyl cysteine (Drug)
结局指标
主要结局
Time to one of the following composite endpoint criteria: 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplant or death from any cause.
时间窗: 24 months
This is a composite endpoint of time to 10% relative decline in forced vital capacity (FVC), first respiratory hospitalization, lung transplant or death from any cause. Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.
次要结局
- Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 24 months(24 months)
- Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 24 months(24 months)
- Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 24 months(24 months)
- Estimated time per six months free of 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause.(24 months)
- Estimated time lived per six months (based on all-cause mortality).(24 months)
- Average time per six months free of first respiratory hospitalization, lung transplantation or death from any cause.(24 months)
- Average time per six months free of 10% relative decline in FVC, lung transplant, or death from any cause.(24 months)
- Average time per six months free of lung transplant, or death from any cause.(24 months)
- Average time per six months free of 10% relative decline in FVC % predicted, lung transplant, or death from any cause.(24 months)
- Average time per six months free of all-cause hospitalization, lung transplant, or death from any cause.(24 months)
- Proportion of participants with and number of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, and unanticipated problems(24 months)
- Estimated time per six months free of 10% relative decline in FVC, first respiratory hospitalization, lung transplant or death from any cause.(24 months)
- Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 24 months(24 months)
- Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 24 months(24 months)
- Change in patient reported outcomes scores for the King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 12 months.(12 months)
- Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 12 months.(12 months)
- Time to one of the following composite criteria: 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause.(24 months)
- Time to death from any cause(24 months)
- Time to first respiratory hospitalization, lung transplant, or death from any cause(24 months)
- Time to 10% relative decline in FVC, lung transplant or death from any cause(24 months)
- Time to lung transplant, or death from any cause(24 months)
- Time to 10% relative decline in FVC %predicted, lung transplant, or death from any cause(24 months)
- Time to first all-cause hospitalization, lung transplant, or death from any cause(24 months)
- Annualized rate of respiratory hospitalizations(24 months)
- Annualized rate of non-elective, all-cause hospitalizations(24 months)
- Absolute change in FVC % predicted from randomization at 12 months(12 months)
- Absolute change in FVC % predicted from randomization at 24 months(24 months)
- Absolute change in FVC from randomization at 12 months(12 months)
- Absolute change in FVC from randomization at 24 months(24 months)
- Absolute change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months(12 months)
- Absolute change in DLCO uncorrected from randomization at 24 months(24 months)
- Absolute change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months.(12 months)
- Absolute change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 12 months.(12 months)
- Change in patient reported outcomes scores for the University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 12 months.(12 months)
研究者
Fernando J Martinez
Professor
University of Massachusetts, Worcester