Sildenafil for Early Pulmonary Vascular Disease in Scleroderma

Inclusion Criteria:

• Previous documentation of mean pulmonary artery pressure between 21 and 24 mm Hgwith a pulmonary capillary wedge pressure (or left ventricular end-diastolicpressure) ≤ 15 mm Hg within six months before study entry.

• Diagnosis of SSc according to 2013 American College of Rheumatology/ European LeagueAgainst Rheumatism (ACR/EULAR) classification criteria.

• Pulmonary function tests with forced expiratory volume in one second/forced vitalcapacity (FEV1/FVC) >50% AND either a) total lung capacity (TLC) or forced vitalcapacity (FVC) > 70% predicted or b) TLC or FVC between 60% and 70% predicted withno more than mild interstitial lung disease on computerized tomography scan of thechest on studies obtained within 6 months of enrollment.

• Ventilation perfusion scan or computed tomography with intravenous contrast (CTangiogram) without evidence of chronic thromboembolism at anytime before studyentry.

• Ability to perform six minute walk testing without significant limitations inmusculoskeletal function or coordination.

• Informed consent.

Exclusion Criteria:

• World Health Organization (WHO) Class IV functional status.

• Systolic blood pressure less than 90 mmHg at screening visit prior to enrollment.

• Clinically significant untreated sleep apnea.

• Left-sided valvular disease (more than moderate mitral valve stenosis orinsufficiency or aortic stenosis or insufficiency), pulmonary artery or valvestenosis, or ejection fraction < 45% on most recent echocardiography (within 1year).

• Use of Pulmonary Arterial Hypertension (PAH) therapy (prostacyclin analogues,endothelin-1 receptor antagonists,phosphodiesterase-5 inhibitors, riociguat,selexipag) within the past 3 months.

• Hospitalized or acutely ill.

• Renal failure (creatinine above 2.0) at screening visit.

• Enrollment in a clinical trial or concurrent use of another investigational drug (non FDA approved) or device therapy within 30 days of screening visit.

• Age < 18.

• Currently pregnant.

• Current use of nitrates.