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CleanUP IPF for the Pulmonary Trials Cooperative (CleanUp-IPF)

Primary Purpose

Idiopathic Pulmonary Fibrosis

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Antimicrobial therapy: Co-trimoxazole or Doxycycline
No Intervention: Standard of Care
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Idiopathic Pulmonary Fibrosis focused on measuring Idiopathic Pulmonary Fibrosis, IPF, pulmonary fibrosis, antimicrobial therapy, doxycycline, co-trimoxazole

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Alabama at Birmingham
  • University of Arizona
  • University of California Davis Medical Center
  • Stanford
  • Loyola University Chicago
  • Northwestern University
  • University of Chicago
  • University of Kansas
  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • Beth Israel Deaconess Medical Center
  • University of Michigan
  • Spectrum Health
  • University of Minnesota
  • Dartmouth-Hitchcock Medical Center
  • Albany Medical College
  • Columbia University
  • Weill Cornell Medicine
  • University of Rochester
  • Mayo Clinic
  • University of Cincinnati
  • Cleveland Clinic
  • Ohio State
  • Pennsylvania State University
  • Temple University
  • Vanderbilt
  • University of Texas at San Antonio
  • University of Utah
  • University of Virginia
  • INOVA
  • Washington University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

Antimicrobial therapy

Standard of care

Arm Description

Co-trimoxazole OR doxycycline

Standard of care for patients with IPF for comparison

Outcomes

Primary Outcome Measures

Number of Participants With First Non-elective, Respiratory Hospitalization or All-cause Mortality

Secondary Outcome Measures

Number of Participants With Death From Any Cause
Number of Participants With First Non-elective, Respiratory Hospitalization
Number of Participants With First Non-elective, All-cause Hospitalization
Total Number of Non-elective Respiratory Hospitalizations
Total Number of Non-elective All-cause Hospitalizations
Percent Change in Forced Vital Capacity (FVC)
Percent Change in Diffusion Capacity of Lungs for Carbon Monoxide (DLCO)
Total Number of Respiratory Infections
Change in UCSD-Shortness of Breath Questionnaire
Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (0 - 120 range). A lower score indicates a better health score. The UCSD-Shortness of Breath Questionnaire assesses the severity of shortness of breath during specific activities of daily living.
Change in Fatigue Severity Scale Score
Fatigue Severity Scale score (1 - 7 range). A lower score indicates a better health score. The Fatigue Severity Scale measures the severity of fatigue and its effect on a person's activities and lifestyle.
Change in Leicester Cough Questionnaire Score
Leicester Cough Questionnaire score (3 - 21 range). A higher score indicates a better health score. The Leicester Cough Questionnaire measures quality of life in people with a chronic cough.
Change in EuroQol Index (EQ-5D) Score
European Quality of Life-5 dimensions (EQ-5D) score (0 - 1 range). A higher score indicates a better health score. The EQ-5D measures quality of life across 5 dimensions (1. Mobility, 2. Self-care, 3. Usual activities, 4. Pain/discomfort, 5. Anxiety/depression.
Change in ICEpop CAPability Measure for Older People (ICECAP-O) Score
Change in ICEpop (Investigating Choice Experiments for the Preferences of Older People) CAPability measure for Older people (ICECAP-O) score (0 - 1 range). A lower score indicates a better health score. The ICEpop CAPability measure for Older people (ICECAP-O) is intended for use in economic evaluations of care services for older people.
Change in Short Form-12 Health Survey (SF-12) 6D Score
Change in Short Form-12 health survey (SF-12) 6D score (0.29 - 1.00 range). A higher indicates a better health score. The SF-12 6D score provides and economic evaluation.
Change in Short Form-12 Health Survey (SF-12) Physical Score
Change in short form-12 health survey (SF-12) physical component summary (PSC) score (0 - 100 range). A higher score indicates a better health score. The short form-12 health survey physical score assesses limitations in physical activities because of health problems.
Change in SF-12 Health Survey (SF-12) Mental Score
Change in short form-12 health survey (SF-12) mental component summary (MCS) score (0 - 100 range). A higher score indicates a better health score. The short form-12 health survey (SF-12) mental component summary (MCS) assesses general mental health.

Full Information

First Posted
April 28, 2016
Last Updated
March 11, 2021
Sponsor
Weill Medical College of Cornell University
Collaborators
Duke Clinical Research Institute, University of Chicago, University of Washington, University of Pittsburgh, National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT02759120
Brief Title
CleanUP IPF for the Pulmonary Trials Cooperative
Acronym
CleanUp-IPF
Official Title
Study of Clinical Efficacy of Antimicrobial Therapy Strategy Using Pragmatic Design in Idiopathic Pulmonary Fibrosis
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Why Stopped
Terminated for futility after review of first planned interim analysis.
Study Start Date
March 22, 2017 (Actual)
Primary Completion Date
March 16, 2020 (Actual)
Study Completion Date
March 16, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
Collaborators
Duke Clinical Research Institute, University of Chicago, University of Washington, University of Pittsburgh, National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Idiopathic Pulmonary Fibrosis
Keywords
Idiopathic Pulmonary Fibrosis, IPF, pulmonary fibrosis, antimicrobial therapy, doxycycline, co-trimoxazole

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
513 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Antimicrobial therapy
Arm Type
Experimental
Arm Description
Co-trimoxazole OR doxycycline
Arm Title
Standard of care
Arm Type
Other
Arm Description
Standard of care for patients with IPF for comparison
Intervention Type
Drug
Intervention Name(s)
Antimicrobial therapy: Co-trimoxazole or Doxycycline
Intervention Description
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
Other
Intervention Name(s)
No Intervention: Standard of Care
Intervention Description
Standard of care
Primary Outcome Measure Information:
Title
Number of Participants With First Non-elective, Respiratory Hospitalization or All-cause Mortality
Time Frame
Randomization to up to 35 months
Secondary Outcome Measure Information:
Title
Number of Participants With Death From Any Cause
Time Frame
Randomization to up to 35 months
Title
Number of Participants With First Non-elective, Respiratory Hospitalization
Time Frame
Randomization to up to 35 months
Title
Number of Participants With First Non-elective, All-cause Hospitalization
Time Frame
Randomization to up to 35 months
Title
Total Number of Non-elective Respiratory Hospitalizations
Time Frame
Randomization to up to 35 months
Title
Total Number of Non-elective All-cause Hospitalizations
Time Frame
Randomization to up to 35 months
Title
Percent Change in Forced Vital Capacity (FVC)
Time Frame
Randomization to 12 months
Title
Percent Change in Diffusion Capacity of Lungs for Carbon Monoxide (DLCO)
Time Frame
Randomization to 12 months
Title
Total Number of Respiratory Infections
Time Frame
Randomization to up to 35 months
Title
Change in UCSD-Shortness of Breath Questionnaire
Description
Change in University of California San Diego (UCSD) Shortness of Breath Questionnaire (0 - 120 range). A lower score indicates a better health score. The UCSD-Shortness of Breath Questionnaire assesses the severity of shortness of breath during specific activities of daily living.
Time Frame
Randomization to 12 months
Title
Change in Fatigue Severity Scale Score
Description
Fatigue Severity Scale score (1 - 7 range). A lower score indicates a better health score. The Fatigue Severity Scale measures the severity of fatigue and its effect on a person's activities and lifestyle.
Time Frame
Randomization to 12 months
Title
Change in Leicester Cough Questionnaire Score
Description
Leicester Cough Questionnaire score (3 - 21 range). A higher score indicates a better health score. The Leicester Cough Questionnaire measures quality of life in people with a chronic cough.
Time Frame
Randomization to 12 months
Title
Change in EuroQol Index (EQ-5D) Score
Description
European Quality of Life-5 dimensions (EQ-5D) score (0 - 1 range). A higher score indicates a better health score. The EQ-5D measures quality of life across 5 dimensions (1. Mobility, 2. Self-care, 3. Usual activities, 4. Pain/discomfort, 5. Anxiety/depression.
Time Frame
Randomization to 12 months
Title
Change in ICEpop CAPability Measure for Older People (ICECAP-O) Score
Description
Change in ICEpop (Investigating Choice Experiments for the Preferences of Older People) CAPability measure for Older people (ICECAP-O) score (0 - 1 range). A lower score indicates a better health score. The ICEpop CAPability measure for Older people (ICECAP-O) is intended for use in economic evaluations of care services for older people.
Time Frame
Randomization to 12 months
Title
Change in Short Form-12 Health Survey (SF-12) 6D Score
Description
Change in Short Form-12 health survey (SF-12) 6D score (0.29 - 1.00 range). A higher indicates a better health score. The SF-12 6D score provides and economic evaluation.
Time Frame
Randomization to 12 months
Title
Change in Short Form-12 Health Survey (SF-12) Physical Score
Description
Change in short form-12 health survey (SF-12) physical component summary (PSC) score (0 - 100 range). A higher score indicates a better health score. The short form-12 health survey physical score assesses limitations in physical activities because of health problems.
Time Frame
Randomization to 12 months
Title
Change in SF-12 Health Survey (SF-12) Mental Score
Description
Change in short form-12 health survey (SF-12) mental component summary (MCS) score (0 - 100 range). A higher score indicates a better health score. The short form-12 health survey (SF-12) mental component summary (MCS) assesses general mental health.
Time Frame
Randomization to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: ≥ 40 years of age Diagnosed with idiopathic pulmonary fibrosis (IPF) by enrolling investigator Signed informed consent Exclusion Criteria: Received antimicrobial therapy in the past 30 days Contraindicated for antibiotic therapy, including but not exclusive to: Allergy or intolerance to both tetracyclines AND trimethoprim, sulfonamides or their combination 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. 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 Allergy or intolerance to tetracyclines AND known glucose-6-phosphate dehydrogenase deficiency Allergy or intolerance to tetracyclines AND untreated folate or B12 deficiency 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. Pregnant or anticipate becoming pregnant 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. Concomitant immunosuppression with azathioprine, mycophenolate, cyclophosphamide, or cyclosporine.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fernando Martinez, MD, MS
Organizational Affiliation
Weill Cornell Medical Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
ZIP/Postal Code
85724
Country
United States
Facility Name
University of California Davis Medical Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Stanford
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Loyola University Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Kansas
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Spectrum Health
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Dartmouth-Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Albany Medical College
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Weill Cornell Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
New York
ZIP/Postal Code
55905
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Ohio State
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43221
Country
United States
Facility Name
Pennsylvania State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Temple University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19122
Country
United States
Facility Name
Vanderbilt
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
INOVA
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Washington University
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All collected IPD will be uploaded in a de-identified manner into BioLINCC with open access for interested investigators
IPD Sharing Time Frame
Within a year of the primary paper publication and then indefinitely maintained by BioLINCC
IPD Sharing Access Criteria
The data will be open access for interested investigators
IPD Sharing URL
https://biolincc.nhlbi.nih.gov/home/
Citations:
PubMed Identifier
33974018
Citation
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.
Results Reference
derived
PubMed Identifier
32164673
Citation
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.
Results Reference
derived

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CleanUP IPF for the Pulmonary Trials Cooperative

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