A Phase 1, Open-Label Study of Intravenous Sildenafil in Patients With Cirrhosis
A Phase 1, Open-Label Study of Intravenous Sildenafil in Patients With Cirrhosis
Safety and tolerability of a single dose intravenous bolus injection of Sildenafil in
 patients with moderate to severe cirrhosis and kidney disease will be determined.
Subjects will be eligible for the study if they meet the following inclusion criteria:

 1. Cirrhosis. Diagnosis of cirrhosis will be based on either liver biopsy OR clinical
 characteristics (e.g. history of ascites or encephalopathy or esophageal varices or
 gastric varices or splenomegaly or spider angioma or any clinical sign of portal
 hypertension/cirrhosis), laboratory (e.g. history of thrombocytopenia or history of
 APRI (Reference: Wai CT, Greenson JK, Fontana RJ, Kalbfleisch JD, Marrero JA,
 Conjeevaram HS, Lok AS. A simple noninvasive index can predict both significant
 fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology
 2003;38:518-26) [Aspartate aminotransferase (AST) to platelet ratio index] score
 consistent with cirrhosis or history of abnormal liver function tests) and abdominal
 imaging (Magnetic Resonance Imaging or Computed Tomography or ultrasound of the
 abdomen) data

 2. CTP Class B or C cirrhosis

 3. Age 18 years or older at the time of enrollment

 4. Variceal screening with an upper endoscopy within 1 year before enrollment

 5. Renal dysfunction [GFR ≥ 15 and < 60 ml/min/1.73m2 estimated by 6-variable MDRD
 equation (Reference: Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S,
 Kusek JW, Van Lente F. Using standardized serum creatinine values in the modification
 of diet in renal disease study equation for estimating glomerular filtration rate. Ann
 Intern Med 2006;145:247-54)]

 6. Hemoglobin level ≥ 8 mg/dl within 4 weeks before enrollment

 7. Serum sodium level ≥ 125 mmol/L within 4 weeks before enrollment

 Subjects will be excluded if they have any of the following:

 1. Inability to provide informed consent

 2. Women who are pregnant, breast-feeding, or contemplating pregnancy

 3. Treatment with organic nitrates, ritonavir, erythromycin, saquinavir, ketoconazole,
 itraconazole, cimetidine, bosentan, rifampin, Sildenafil or any other PDE-5
 inhibitors, alpha-blockers, and anticoagulants within 7 days before enrollment

 4. Hypersensitivity or allergy to Sildenafil or any component of Sildenafil

 5. Previous reaction to PDE-5 inhibitors including, but not limited to Sildenafil,
 Vardenafil, Tadalafil, Avanafil (Myocardial infarction, ventricular arrhythmia, sudden
 cardiac death, cerebrovascular hemorrhage, transient ischemic attack, stroke,
 transient global amnesia, subarachnoid and intracerebral hemorrhages, seizure,
 recurrence in seizures, pulmonary hemorrhage, sudden decrease of hearing, loss of
 hearing, anxiety, prolonged erection, priapism, ocular redness, ocular burning,
 diplopia, temporary vision loss/decreased vision, ocular swelling, ocular pressure,
 increased intraocular pressure, retinal problems in the eye, vitreous detachment,
 vitreous traction, paramacular edema, non-arteritic anterior ischemic optic
 neuropathy)

 6. History of untreated severe left ventricular outflow obstruction (e.g. aortic
 stenosis, idiopathic hypertrophic subaortic stenosis)

 7. History of pulmonary veno-occlusive disease

 8. History of unstable angina, myocardial infarctus, life-threatening arrhythmia or
 stroke within 6 months before enrollment

 9. History of retinitis pigmentosa

 10. Anatomical deformation of the penis (Peyronie's disease, angulation, cavernosal
 fibrosis)

 11. History of sickle cell anemia, multiple myeloma or leukemia

 12. Renal failure treated with dialysis

 13. Cognitive impairment based on IRB "evaluation to sign consent form"

 14. Transjugular intrahepatic porto-systemic shunt placement

 15. Previous kidney or liver transplantation