Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial
- Conditions
- Idiopathic Pulmonary Fibrosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT04300920
- Lead Sponsor
- Weill Medical College of Cornell University
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 202
- ≥ 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description N-acetylcysteine N-acetyl cysteine 600 mg oral N-acetylcysteine (NAC) three times daily for 24 months. Placebo Placebo Placebo tablet three times daily for 24 months.
- Primary Outcome Measures
Name Time Method 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. 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.
- Secondary Outcome Measures
Name Time Method Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 24 months 24 months Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) 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 Change in FVC from randomization at 12 months 12 months Time to death from any cause 24 months Time to first respiratory hospitalization 24 months Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.
Time to first all-cause hospitalization 24 months Annualized rate of respiratory hospitalizations 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 University of California, San Diego Shortness of Breath (UCSD-SOB) Questionnaire from randomization at 24 months 24 months Time to 10% relative decline in FVC 24 months Annualized rate of non-elective, all-cause hospitalizations 24 months Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 24 months 24 months Time to lung transplant 24 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 This is a composite endpoint of time to 10% relative decline in FVC % predicted, based on the global lung initiative (GLI) reference equation, first respiratory hospitalization, lung transplant or death from any cause. Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.
Time to 10% relative decline in FVC %predicted 24 months Proportion of participants undergoing lung transplant during follow-up 24 months Change in FVC % predicted from randomization at 12 months 12 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 King's Brief Interstitial Lung Disease (K-BILD) Questionnaire from randomization at 24 months 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 Change in FVC % predicted from randomization at 24 months 24 months Change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months 12 months Change in DLCO from randomization at 24 months 24 months Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 12 months. 12 months Change in FVC from randomization at 24 months 24 months Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 12 months. 12 months
Trial Locations
- Locations (25)
Piedmont Healthcare
🇺🇸Austell, Georgia, United States
Loyola University
🇺🇸Maywood, Illinois, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Washington
🇺🇸Seattle, Washington, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
Stanford University
🇺🇸Stanford, California, United States
Tulane University
🇺🇸New Orleans, Louisiana, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Weill Cornell Medicine
🇺🇸New York, New York, United States
Ohio State University
🇺🇸Columbus, Ohio, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Temple University
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas Southwestern
🇺🇸Dallas, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
University of Rochester
🇺🇸Rochester, New York, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
Lisa Lancaster
🇺🇸Nashville, Tennessee, United States
University of Texas Health San Antonio
🇺🇸San Antonio, Texas, United States
University of Utah Health
🇺🇸Salt Lake City, Utah, United States
University of Southern California
🇺🇸Los Angeles, California, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States