Clinical trial NCT02759120: CleanUP IPF for the Pulmonary Trials Cooperative
Official title: Study of Clinical Efficacy of Antimicrobial Therapy Strategy Using Pragmatic Design in Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic Pulmonary Fibrosis
IPF
pulmonary fibrosis
antimicrobial therapy
doxycycline
co-trimoxazole
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: Duke Clinical Research Institute
name: University of Chicago
name: University of Washington
name: University of Pittsburgh
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-05-03
Enrollment: 513
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With First Non-elective, Respiratory Hospitalization or All-cause Mortality
timeFrame: Randomization to up to 35 months
Secondary outcomes:
measure: Number of Participants With Death From Any Cause
timeFrame: Randomization to up to 35 months
measure: Number of Participants With First Non-elective, Respiratory Hospitalization
timeFrame: Randomization to up to 35 months
measure: Number of Participants With First Non-elective, All-cause Hospitalization
timeFrame: Randomization to up to 35 months
measure: Total Number of Non-elective Respiratory Hospitalizations
timeFrame: Randomization to up to 35 months
measure: Total Number of Non-elective All-cause Hospitalizations
timeFrame: Randomization to up to 35 months
measure: Percent Change in Forced Vital Capacity (FVC)
timeFrame: Randomization to 12 months
measure: Percent Change in Diffusion Capacity of Lungs for Carbon Monoxide (DLCO)
timeFrame: Randomization to 12 months
measure: Total Number of Respiratory Infections
timeFrame: Randomization to up to 35 months
measure: Change in UCSD-Shortness of Breath Questionnaire
timeFrame: Randomization to 12 months
measure: Change in Fatigue Severity Scale Score
timeFrame: Randomization to 12 months
measure: Change in Leicester Cough Questionnaire Score
timeFrame: Randomization to 12 months
measure: Change in EuroQol Index (EQ-5D) Score
timeFrame: Randomization to 12 months
measure: Change in ICEpop CAPability Measure for Older People (ICECAP-O) Score
timeFrame: Randomization to 12 months
measure: Change in Short Form-12 Health Survey (SF-12) 6D Score
timeFrame: Randomization to 12 months
measure: Change in Short Form-12 Health Survey (SF-12) Physical Score
timeFrame: Randomization to 12 months
measure: Change in SF-12 Health Survey (SF-12) Mental Score
timeFrame: Randomization to 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: Stanford
country: United States
facility: Stanford
state: California
city: Chicago
country: United States
facility: Loyola University Chicago
state: Illinois
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas
state: Kansas
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Grand Rapids
country: United States
facility: Spectrum Health
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Rochester
country: United States
facility: Mayo Clinic
state: New York
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State
state: Ohio
city: Hershey
country: United States
facility: Pennsylvania State University
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: San Antonio
country: United States
facility: University of Texas at San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Falls Church
country: United States
facility: INOVA
state: Virginia
city: Seattle
country: United States
facility: Washington University
state: Washington
Study officials:
affiliation: Weill Cornell Medical Medicine
name: Fernando Martinez, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.