Evaluation and Treatment of Pulmonary Vascular Disease in Moderate to Severe CF

Inclusion Criteria:

1. Confirmed diagnosis of CF based on the following criteria: Positive sweat chloride ≥60mEq/liter (by pilocarpine iontophoresis) and/or Genotype with two identifiable mutations consistent with CF, and accompanied by one or more clinical features consistent with the CF phenotype
2. Male or female patients ≥ 18 years of age
3. FEV1 ≥ 20% predicted and ≤ 70% predicted (Hankinson)
4. Clinically stable without evidence of acute upper or lower respiratory tract infection or current pulmonary exacerbation within the 14 days prior to the screening visit
5. Ability to reproducibly perform spirometry (according to ATS criteria)
6. Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
7. Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled antibiotics)

Exclusion Criteria:

1. History of hypersensitivity to sildenafil
2. Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
3. Breastfeeding, pregnant, or verbal expression of unwillingness to practice an acceptable birth control method (abstinence, hormonal or barrier methods, partner sterilization or intrauterine device) during participation in the study for women of child-bearing potential.
4. History of significant hepatic disease (AST or ALT > 5 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension),
5. History of significant cardiovascular disease (history of aortic stenosis, coronary artery disease, or life-threatening arrhythmia),
6. History of severe neurological disease (e.g. history of stroke),
7. History of severe hematologic disease (e.g. history of bleeding diathesis; current INR > 2.0
8. History of severe ophthalmologic disease (e.g. history of retinal impairment or non-arteritic ischemic optic neuritis)
9. History of severe renal impairment (creatinine >1.8 mg/dL.)
10. Inability to swallow pills
11. Previous organ transplantation
12. Use of concomitant nitrates, α-blocker, or Ca channel blocker (currently or within one month of Visit 1)
13. Use of concomitant medications known to be potent inhibitors of CYP3A4 [e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin (currently or within one month of initiation of study drug)] NOTE: use of azithromycin is NOT a cause for exclusion
14. History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacterium massiliense within 2 years of screening
15. Weight less than 40 kg at Screening
16. History of migraine headaches.
17. Resting room air oxygen saturation <80% without supplemental oxygen
18. Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the subject or the quality of the data
19. Start of CFTR modulator therapy less than 1 month prior to first dose of sildenafil or placebo
20. Use of anticoagulants
21. Frank pulmonary hypertension (RVSP >40 mmHg by ECHO)