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

NCT04300920 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: 19-120212321U24HL145265-01A1
• Study Type: interventional
• Target: 202
• Locations: 1 country
• Sites: 25

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.

Conditions

Idiopathic Pulmonary Fibrosis

Keywords

IPF; Pulmonary Fibrosis; n-acetylcysteine; NAC

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (34)

• 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

Study Arms (2)

N-acetylcysteine

EXPERIMENTAL

600 mg oral N-acetylcysteine (NAC) three times daily for 24 months.

Drug: N-acetyl cysteine

Placebo

PLACEBO COMPARATOR

Placebo tablet three times daily for 24 months.

Drug: Placebo

Interventions

N-acetyl cysteine DRUG

600 mg N-acetylcysteine (NAC) oral tablets three times daily for 24 months.

Also known as: NAC

N-acetylcysteine

Placebo DRUG

Matching oral placebo tablet three times daily for 24 months.

Placebo

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fernando J Martinez: lead
• University of Virginia: collaborator
• University of Michigan: collaborator
• Pulmonary Fibrosis Foundation: collaborator
• University of Washington: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Three Lakes Foundation: collaborator

Study Sites (25)

University of Arizona

Tucson, Arizona, 85724, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Piedmont Healthcare

Austell, Georgia, 30106, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Loyola University

Maywood, Illinois, 60153, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Tulane University

New Orleans, Louisiana, 70112, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Weill Cornell Medicine

New York, New York, 10016, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Ohio State University

Columbus, Ohio, 43221, United States

Location

Temple University

Philadelphia, Pennsylvania, 19140, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Lisa Lancaster

Nashville, Tennessee, 37204, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

University of Texas Health San Antonio

San Antonio, Texas, 78229, United States

Location

University of Utah Health

Salt Lake City, Utah, 84108, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (1)

• Podolanczuk AJ, Kim JS, Cooper CB, Lasky JA, Murray S, Oldham JM, Raghu G, Flaherty KR, Spino C, Noth I, Martinez FJ; PRECISIONS Study Team. Design and rationale for the prospective treatment efficacy in IPF using genotype for NAC selection (PRECISIONS) clinical trial. BMC Pulm Med. 2022 Dec 13;22(1):475. doi: 10.1186/s12890-022-02281-8.

  PMID: 36514019 DERIVED

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Pulmonary Fibrosis

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Fernando J Martinez, MD

  University of Massachusetts Chan Medical School

  PRINCIPAL INVESTIGATOR

• Imre Noth, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

• Kevin Flaherty, MS, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

• Cathie Spino, ScD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant and site personnel will not know which study treatment the participant is receiving.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: 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 three times daily or matched placebo for 24 months.

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 9, 2020
• Study Start: December 17, 2020
• Primary Completion: March 2, 2026
• Study Completion: March 2, 2026
• Last Updated: March 20, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• Access Criteria: Data will be shared through the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).

Locations

US (25)