Safety and Efficacy of Sildenafil in Cystic Fibrosis (CF) Lung Disease

The purpose of this study is to determine whether sildenafil can decrease inflammation in CF lung disease.

This study is an open-label study that examines the use of sildenafil (Revatio) in clinically stable patients with mild to moderate CF lung disease. The length of participation for each subject will be approximately 10 weeks, and will consist of a screening visit, a study visit for initiation of study drug if subject qualifies, interim visits to escalate drug dose, obtain drug levels, review concomitant medications and assess side effects, a visit at the end of the therapy period (to reassess inflammatory markers, laboratory studies and side effects,) and a follow-up assessment 2 weeks after subject completion.

Eligibility Criteria:
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 ≥ 12 years of age
* FEV1 ≥ 50% predicted (Knudson) 31
* 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 produce at least 1mL of sputum spontaneously, or be willing to undergo sputum induction
* Ability to understand and sign a written informed consent or assent and comply with the requirements of the study
* Chronic bacterial colonization (3 documented positive cultures in the prior 2 years of which at least one was obtained in the 3 months prior to randomization)

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
* Daily use of systemic corticosteroids and/or NSAIDs within 4 weeks of the study or as needed use within 72 hours prior to the screening visit
* History of significant hepatic (SGOT or SGPT \> 3 times the upper limit of normal at screening, documented biliary cirrhosis, or portal hypertension), cardiovascular (history of aortic stenosis, coronary artery disease, pulmonary hypertension with right ventricular systolic pressure \>55 mmHg or life-threatening arrhythmia), neurological (history of stroke), hematologic (history of bleeding diathesis), ophthalmologic (history of retinal impairment or non-arteritic ischemic optic neuritis) or renal impairment (creatinine \>1.8 mg/dL.)
* Inability to swallow pills
* Previous lung transplantation
* Use of concomitant nitrates, α-blocker, or Ca channel blocker
* Use of concomitant medications known to be potent inhibitors of CYP3A4 (e.g. ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin, rifampin)
* 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
* Weight less than 40 kg
* History of sputum or throat swab culture yielding Burkholderia cepacia within 2 years of screening
* Resting room air oxygen saturation \<93%
* History of migraines