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

January 31, 2024 updated by: Weill Medical College of Cornell University

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

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • 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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: N-acetylcysteine
600 mg oral N-acetylcysteine (NAC) three times daily for 24 months.
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.
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.
Time Frame: 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.
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.
Time Frame: 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.
24 months
Time to death from any cause
Time Frame: 24 months
24 months
Time to first respiratory hospitalization
Time Frame: 24 months
Respiratory hospitalizations will be determined by a blinded clinical events classification (adjudication) committee.
24 months
Time to 10% relative decline in FVC
Time Frame: 24 months
24 months
Time to lung transplant
Time Frame: 24 months
24 months
Time to 10% relative decline in FVC %predicted
Time Frame: 24 months
24 months
Time to first all-cause hospitalization
Time Frame: 24 months
24 months
Annualized rate of respiratory hospitalizations
Time Frame: 24 months
24 months
Annualized rate of non-elective, all-cause hospitalizations
Time Frame: 24 months
24 months
Proportion of participants undergoing lung transplant during follow-up
Time Frame: 24 months
24 months
Change in FVC from randomization at 12 months
Time Frame: 12 months
12 months
Change in FVC % predicted from randomization at 12 months
Time Frame: 12 months
12 months
Change in FVC from randomization at 24 months
Time Frame: 24 months
24 months
Change in FVC % predicted from randomization at 24 months
Time Frame: 24 months
24 months
Change in diffusing capacity of the lung for carbon monoxide (DLCO) uncorrected for hemoglobin from randomization at 12 months
Time Frame: 12 months
12 months
Change in DLCO from randomization at 24 months
Time Frame: 24 months
24 months
Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 12 months.
Time Frame: 12 months
12 months
Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 12 months.
Time Frame: 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.
Time Frame: 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.
Time Frame: 12 months
12 months
Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 12 months.
Time Frame: 12 months
12 months
Change in patient reported outcomes scores for the Leicester Cough Questionnaire (LCQ) from randomization at 24 months
Time Frame: 24 months
24 months
Change in patient reported outcomes scores for the EuroQoL EQ-5D Questionnaire from randomization at 24 months
Time Frame: 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
Time Frame: 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
Time Frame: 24 months
24 months
Change in patient reported outcomes scores for the St. George's Respiratory Questionnaire (SGRQ) from randomization at 24 months
Time Frame: 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
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

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

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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