CleanUP IPF for the Pulmonary Trials Cooperative

NCT ID: NCT02759120

Last Updated: 2021-04-08

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

513 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-03-22

Study Completion Date

2020-03-16

Brief Summary

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The purpose of this study is to compare the effect of standard care, versus standard of care plus antimicrobial therapy (co-trimoxazole or doxycycline), on clinical outcomes in patients diagnosed with idiopathic pulmonary fibrosis (IPF).

Detailed Description

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This is a randomized, un-blinded, phase III, multi-center clinical trial of an antimicrobial therapy strategy in idiopathic pulmonary fibrosis patients. Our overall hypothesis is that reducing harmful microbial impact with antimicrobial therapy will reduce the risk of non-elective, respiratory hospitalization or death in patients with Idiopathic Pulmonary Fibrosis (IPF).

Subjects will be randomized 1:1 to either receive a prescription drug voucher for oral antimicrobial therapy in the form of one double strength 160 milligrams (mg) trimethoprim/800mg sulfamethoxazole (double strength co-trimoxazole) twice daily plus folic acid 5 mg daily OR doxycycline 100mg once daily if weight \< 50 kilograms (kg) or 100mg twice daily if weight \> 50 kg. Patients randomized to receive antimicrobial therapy will be given co-trimoxazole unless they have an allergy, contraindication to co-trimoxazole, renal insufficiency (glomerular filtration rate (GFR) \< 30 milliliters (ml)), are hyperkalemic (potassium \> 5 milliequivalents(mEq)/liter(L)), or are concomitantly taking an angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or potassium sparing diuretic in which case they will receive doxycycline.

Participation in this study will be between 12 months and 36 months depending on time of enrollment.

Conditions

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Idiopathic Pulmonary Fibrosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Antimicrobial therapy

Co-trimoxazole OR doxycycline

Group Type EXPERIMENTAL

Antimicrobial therapy: Co-trimoxazole or Doxycycline

Intervention Type DRUG

160mg trimethoprim/800mg sulfamethoxazole (double strength co-trimoxazole) twice daily plus folic acid 5 mg daily OR doxycycline 100mg once daily if weight \< 50 kilograms or 100mg twice daily if weight \> 50 kilograms for up to 36 months

Standard of care

Standard of care for patients with IPF for comparison

Group Type OTHER

No Intervention: Standard of Care

Intervention Type OTHER

Standard of care

Interventions

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Antimicrobial therapy: Co-trimoxazole or Doxycycline

160mg trimethoprim/800mg sulfamethoxazole (double strength co-trimoxazole) twice daily plus folic acid 5 mg daily OR doxycycline 100mg once daily if weight \< 50 kilograms or 100mg twice daily if weight \> 50 kilograms for up to 36 months

Intervention Type DRUG

No Intervention: Standard of Care

Standard of care

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. ≥ 40 years of age
2. Diagnosed with idiopathic pulmonary fibrosis (IPF) by enrolling investigator
3. Signed informed consent

Exclusion Criteria

1. Received antimicrobial therapy in the past 30 days
2. Contraindicated for antibiotic therapy, including but not exclusive to:

1. Allergy or intolerance to both tetracyclines AND trimethoprim, sulfonamides or their combination
2. Allergy or intolerance to tetracyclines AND known potassium level \> 5 mEq/L in the past 90 days.

* If the enrolling physician feels the potassium level has normalized, documentation to that effect must be provided.
3. Allergy or intolerance to tetracyclines AND concomitant use of angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), potassium sparing diuretic, dofetilide, methotrexate, azathioprine, mycophenolate mofetil, cyclophosphamide
4. Allergy or intolerance to tetracyclines AND known glucose-6-phosphate dehydrogenase deficiency
5. Allergy or intolerance to tetracyclines AND untreated folate or B12 deficiency
6. Allergy or intolerance to tetracyclines AND known renal insufficiency (defined as a glomerular filtration rate (GFR) \< 30 ml within the previous 90 days)

* If the enrolling physician feels the renal dysfunction has resolved, documentation to that effect must be provided.
3. Pregnant or anticipate becoming pregnant
4. Use of an investigational study agent for IPF therapy within the past 30 days, or an IV infusion with a half-life of four (4) weeks.
5. Concomitant immunosuppression with azathioprine, mycophenolate, cyclophosphamide, or cyclosporine.
Minimum Eligible Age

40 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke Clinical Research Institute

OTHER

Sponsor Role collaborator

University of Chicago

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role collaborator

University of Pittsburgh

OTHER

Sponsor Role collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Fernando Martinez, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Weill Cornell Medical Medicine

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

University of Arizona

Tucson, Arizona, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

Stanford

Stanford, California, United States

Site Status

Loyola University Chicago

Chicago, Illinois, United States

Site Status

Northwestern University

Chicago, Illinois, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

University of Kansas

Kansas City, Kansas, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Spectrum Health

Grand Rapids, Michigan, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

University of Rochester

Rochester, New York, United States

Site Status

Mayo Clinic

Rochester, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Cleveland Clinic

Cleveland, Ohio, United States

Site Status

Ohio State

Columbus, Ohio, United States

Site Status

Pennsylvania State University

Hershey, Pennsylvania, United States

Site Status

Temple University

Philadelphia, Pennsylvania, United States

Site Status

Vanderbilt

Nashville, Tennessee, United States

Site Status

University of Texas at San Antonio

San Antonio, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

University of Virginia

Charlottesville, Virginia, United States

Site Status

INOVA

Falls Church, Virginia, United States

Site Status

Washington University

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Kim JS, Murray S, Yow E, Anstrom KJ, Kim HJ, Flaherty KR, Martinez FJ, Noth I. Comparison of Pirfenidone and Nintedanib: Post Hoc Analysis of the CleanUP-IPF Study. Chest. 2024 May;165(5):1163-1173. doi: 10.1016/j.chest.2023.11.035. Epub 2023 Nov 27.

Reference Type DERIVED
PMID: 38030064 (View on PubMed)

Martinez FJ, Yow E, Flaherty KR, Snyder LD, Durheim MT, Wisniewski SR, Sciurba FC, Raghu G, Brooks MM, Kim DY, Dilling DF, Criner GJ, Kim H, Belloli EA, Nambiar AM, Scholand MB, Anstrom KJ, Noth I; CleanUP-IPF Investigators of the Pulmonary Trials Cooperative. Effect of Antimicrobial Therapy on Respiratory Hospitalization or Death in Adults With Idiopathic Pulmonary Fibrosis: The CleanUP-IPF Randomized Clinical Trial. JAMA. 2021 May 11;325(18):1841-1851. doi: 10.1001/jama.2021.4956.

Reference Type DERIVED
PMID: 33974018 (View on PubMed)

Anstrom KJ, Noth I, Flaherty KR, Edwards RH, Albright J, Baucom A, Brooks M, Clark AB, Clausen ES, Durheim MT, Kim DY, Kirchner J, Oldham JM, Snyder LD, Wilson AM, Wisniewski SR, Yow E, Martinez FJ; CleanUP-IPF Study Team. Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy - the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial. Respir Res. 2020 Mar 12;21(1):68. doi: 10.1186/s12931-020-1326-1.

Reference Type DERIVED
PMID: 32164673 (View on PubMed)

Provided Documents

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Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

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U01HL128954

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1504016087

Identifier Type: -

Identifier Source: org_study_id

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