Double-Blind, Randomised, Parallel-Group, Placebo-Controlled, Multi-Centre Phase II Clinical Study on the Efficacy and Safety of Different Doses of Udenafil in Cirrhotic Patients with Portal Hypertension Preceded by an Open-Label Pilot Phase - Udenafil tablets vs. placebo in portal hypertensio

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 220

Inclusion Criteria

1. Signed informed consent.
2. Man or woman between 18 and 70 years of age.
3. Compensated liver cirrhosis as proven by clinical findings, laboratory tests, and ultrasound.
4. Liver cirrhosis as proven by histology (histology within 5 years prior to Baseline visit) or FibroScan (facultative) or by unequivocal clinical, radiological and laboratory signs.
5. Clinically significant portal hypertension defined as HVPG = 12 mm Hg.
6. Low risk of bleeding characterized by no or small (< 5 mm in diameter) oesophageal varices proven by endoscopy (previous full variceal banding ligation or obliterative sclerotherapy as primary or secondary prophylaxis for variceal haemorrhage allowed).
7. Women of child-bearing potential have to apply double barrier methods of contraception (e.g. oral contraception with condom). The investigator is responsible for determining whether the patient has adequate birth control for study participation.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Child-Pugh C.
2. Existing transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunt.
3. Splenic or portal vein thrombosis by Doppler ultrasonography, magnetic resonance imaging.
4. Gastric/duodenal varices with bleeding stigmata (red colour sign or clot) or gastric/duodenal varices with history of bleeding.
5. Large oesophageal varices (= 5 mm in diameter).
6. Alcoholic hepatitis.
7. Hepatic encephalopathy = stage 2.
8. Ascites present at Baseline visit.
9. Total Bilirubin > 3 mg/dl.
10. Bleeding disorder, INR > 2.
11. Active peptic ulceration.
12. Open-label pilot phase only: Positive Hepatitis B or C serology
13. Positive HIV serology
14. Anatomical deformation of the penis or penile implants.
15. Predisposing priapism, sickle cell anaemia or trait, thrombocythaemia, polycythaemia, prone to venous thrombosis (immobility, surgery of pelvis, abdomen, hip, thrombophilia, history of thrombosis etc.), hyperviscosity syndrome (increased blood viscosity in particular due to polymers typical in multiple myeloma, polycythemia vera, Raynaud’s phenomenon, Waldenström’s macroglobulinemia).
16. Known hereditary degenerative retinal disorders, including retinitis pigmentosa.
17. Previous episode of NAION.
18. Renal failure (GFR < 60 ml/min/1.73 m²).
19. QTc prolongation (QTc>440 ms) or treatment with QTc interval-increasing medications.
20. Heart failure (NYHA II-IV).
21. Angina pectoris.
22. History of myocardial infarction, stroke or life-threatening arrhythmia.
23. Aortic stenosis.
24. Resting hypotension (systolic blood pressure [SBP]/diastolic blood pressure [DBP] < 90/60 mm Hg), uncontrolled hypertension (SBP/DBP > 170/100 mm Hg).
25. Symptomatic hypotension (e.g. fainting) following alpha-blocker administration.
26. Bacterial infection (positive blood, urine or ascites cultures; or ascites with leucocytes = 500/µl or PMN = 250/µl) within 2 weeks prior to Baseline visit.
27. Drugs that may have an effect on splanchnic haemodynamics/portal pressure, e.g. ß-blockers, clonidine, prazosin, nitrates, and any other antihypertensive treatment within 2 weeks prior to Baseline visit (Exception: losartan within 4 weeks prior to Baseline visit).
28. Concomitant treatment with ß-blockers, calcium channel blockers, clonidine, prazosin, nitrates, molsidomine, any antihypertensive treatment and any drug which may have an effect on splanchnic haemodynamics/portal pressure.
29. Concomitant treatment with vasopressin or somatostatin and their derivatives and analogues.
30. Concomitant treatment with platelet aggregation inhibitors, e.g. aspirin, heparin.
31. Concomitant treatment with other PDE-5 inhibitors, e.g. sildenafil, tadalafil or vardenafil.
32. Treatment with ketoconazole or other CYP3A inhibitors or inducers, consumption of grapefruit juice.
33. Active hepatocellular cancer or a history of hepatocellular cancer (to be excluded by ultrasound and tumour markers).
34. Active malignancy other than hepatocellular cancer or treatment with anticancer drugs during the last 5 years. Patients with a history of cancer other than hepatocellular cancer and at least five years of uneventful follow up and no signs of recurrence may be eligible.
35. Severe co-morbidity substantially reducing life expectancy.
36. Known intolerance/hypersensitivity/resistance to study drug or drugs of similar chemical structure or pharmacological profile.
37. Doubt about the patient’s cooperation, e.g. because of addiction to alcohol or drugs.
38. Existing or intended

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials

Different doses of Udenafil tablets against portal hypertension for patients with liver cirrhosis

Dr. Falk Pharma GmbH

Updated 12/3/2012