CleanUP IPF for the Pulmonary Trials Cooperative

Study Overview
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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.

Official Title
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Study of Clinical Efficacy of Antimicrobial Therapy Strategy Using Pragmatic Design in Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: Antimicrobial therapy: Co-trimoxazole or Doxycycline
* Other: No Intervention: Standard of Care


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antimicrobial therapy<br>Co-trimoxazole OR doxycycline | Drug: Antimicrobial therapy: Co-trimoxazole or Doxycycline<br>* 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<br>|
| Other: Standard of care<br>Standard of care for patients with IPF for comparison | Other: No Intervention: Standard of Care<br>* Standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With First Non-elective, Respiratory Hospitalization or All-cause Mortality |  | Randomization to up to 35 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Death From Any Cause |  | Randomization to up to 35 months | 
| Number of Participants With First Non-elective, Respiratory Hospitalization |  | Randomization to up to 35 months | 
| Number of Participants With First Non-elective, All-cause Hospitalization |  | Randomization to up to 35 months | 
| Total Number of Non-elective Respiratory Hospitalizations |  | Randomization to up to 35 months | 
| Total Number of Non-elective All-cause Hospitalizations |  | Randomization to up to 35 months | 
| Percent Change in Forced Vital Capacity (FVC) |  | Randomization to 12 months | 
| Percent Change in Diffusion Capacity of Lungs for Carbon Monoxide (DLCO) |  | Randomization to 12 months | 
| Total Number of Respiratory Infections |  | Randomization to up to 35 months | 
| 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. | Randomization to 12 months | 
| 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. | Randomization to 12 months | 
| 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. | Randomization to 12 months | 
| 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. | Randomization to 12 months | 
| 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. | Randomization to 12 months | 
| 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. | Randomization to 12 months | 
| 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. | Randomization to 12 months | 
| 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. | Randomization to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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doxycycline, IPF, Idiopathic Pulmonary Fibrosis, pulmonary fibrosis, antimicrobial therapy, co-trimoxazole