CleanUP IPF for the Pulmonary Trials Cooperative

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.

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.