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

Inclusion Criteria

• 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
• Male or female patients ≥ 18 years of age
• FEV1 ≥ 20% predicted and ≤ 70% predicted (Hankinson)
• 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
• Ability to reproducibly perform spirometry (according to ATS criteria)
• Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
• Willingness to maintain chronic CF medication schedule (e.g. alternating month inhaled antibiotics)

Exclusion Criteria

• History of hypersensitivity to sildenafil
• Use of an investigational agent within the 4-week period prior to Visit 1 (Day 0)
• 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.
• History of significant hepatic disease (AST or ALT > 5 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension),
• History of significant cardiovascular disease (history of aortic stenosis, coronary artery disease, or life-threatening arrhythmia),
• History of severe neurological disease (e.g. history of stroke),
• History of severe hematologic disease (e.g. history of bleeding diathesis; current INR > 2.0
• History of severe ophthalmologic disease (e.g. history of retinal impairment or non-arteritic ischemic optic neuritis)
• History of severe renal impairment (creatinine >1.8 mg/dL.)
• Inability to swallow pills
• Previous organ transplantation
• Use of concomitant nitrates, α-blocker, or Ca channel blocker (currently or within one month of Visit 1)
• 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
• History of sputum or throat swab culture yielding Burkholderia cepacia or Mycobacterium massiliense within 2 years of screening
• Weight less than 40 kg at Screening
• History of migraine headaches.
• Resting room air oxygen saturation 40 mmHg by ECHO)