Prospective Treatment Efficacy in IPF Using Genotype for Nac Selection (PRECISIONS) Trial (PRECISIONS)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: N-acetyl cysteine; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Betsy Peters; Phone Number: 646-962-2742; Email: elp2018@med.cornell.edu

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Stanford, California, United States, 94305
      • Stanford University
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • Georgia
    • Austell, Georgia, United States, 30106
      • Piedmont Healthcare
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Maywood, Illinois, United States, 60153
      • Loyola University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • New York
    • New York, New York, United States, 10016
      • Weill Cornell Medicine
    • Rochester, New York, United States, 14642
      • University of Rochester
  • Ohio
    • Columbus, Ohio, United States, 43221
      • Ohio State University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Lisa Lancaster
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern
    • San Antonio, Texas, United States, 78229
      • University of Texas Health San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah Health
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• ≥ 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-acetylcysteine; 600 mg oral N-acetylcysteine (NAC) three times daily for 24 months.	Drug: N-acetyl cysteine; 600 mg N-acetylcysteine (NAC) oral tablets three times daily for 24 months.; Other Names: NAC
Placebo Comparator: Placebo; Placebo tablet three times daily for 24 months.	Drug: Placebo; Matching oral placebo tablet three times daily for 24 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to one of the following composite criteria: 10% relative decline in FVC % predicted, first respiratory hospitalization, lung transplant or death from any cause.	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.	24 months
Time to death from any cause		24 months
Time to first respiratory hospitalization	Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.	24 months
Time to 10% relative decline in FVC		24 months
Time to lung transplant		24 months
Time to 10% relative decline in FVC %predicted		24 months
Time to first all-cause hospitalization		24 months
Annualized rate of respiratory hospitalizations		24 months
Annualized rate of non-elective, all-cause hospitalizations		24 months
Proportion of participants undergoing lung transplant during follow-up		24 months
Change in FVC from randomization at 12 months		12 months
Change in FVC % predicted from randomization at 12 months		12 months
Change in FVC from randomization at 24 months		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 Leicester Cough Questionnaire (LCQ) from randomization at 12 months.		12 months
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
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
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 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
Proportion of participants with and number of treatment-emergent adverse events, serious adverse events, adverse events leading to discontinuation, and unanticipated problems		24 months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Michigan; University of Washington; University of Virginia; Pulmonary Fibrosis Foundation; Three Lakes Foundation
• Investigators: Principal Investigator: Cathie Spino, ScD, University of Michigan; Principal Investigator: Fernando J Martinez, MD, Weill Medical College of Cornell University; Principal Investigator: Imre Noth, MD, University of Virginia; Principal Investigator: Kevin Flaherty, MS, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): December 17, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 6, 2020
• First Submitted That Met QC Criteria: March 6, 2020
• First Posted (Actual): March 9, 2020

Study Record Updates

• Last Update Posted (Estimated): February 2, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: NAC; n-acetylcysteine; IPF; Pulmonary Fibrosis
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Interstitial; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: 19-12021232; 1U24HL145265-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The de-identified analytic data will be prepared as SAS transport files or ASCII comma-delimited files with accompanying codebooks that describe the data and data structure. The redaction will employ best practices and will be consistent with NHLBI data sharing policies.
• IPD Sharing Time Frame: 3 years after the end of the study or 2 years after the main paper reporting the results of the trial, whichever comes first.
• IPD Sharing Access Criteria: Data will be shared through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No