Portal hypertension, liver cirrhosis
Conditions
Interventions
Product Name: Udenafil
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Udenafil
Concentration unit: mg milligram(s)
Concentration number: 50-
Pharmaceutical form of the placebo: Film-coat
Sponsors
STZ 1172 Gesundheitsförderung und Stoffwechselforschung
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed informed consent. 2.Man or woman between 18 and 70 years of age. 3.Liver cirrhosis as proven by clinical findings, laboratory tests, and ultrasound. 4.One of the following: a)HVPG = 10 mm Hg measured within the last 24 months or b)Varices proven by endoscopy or c)Varices with history of bleeding (but: no bleeding within the last 4 weeks before baseline) or d)Ascites or e)Anamnestic ascites. 5.Women of child-bearing potential have to apply double barrier methods of contraception (e.g. oral contraception with condom) or a highly effective method of birth control which is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptive method, some IUDs, sexual abstinence or vasectomised partner. 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Child-Pugh C. 2.Existing transjugular intrahepatic portosystemic shunt (TIPS) or surgical shunt. 3.Splenic, mesenteric or portal vein thrombosis by Doppler ultrasonography, magnetic resonance imaging. 4.Retrograde perfusion in portal vein or both branches, collateral blood flow more than 1/3 of the volume of portal blood flow 5.Hepatic encephalopathy = stage 2. 6.Total Bilirubin > 3.5 mg/dl. 7.Bleeding disorder, INR > 2. 8.Active peptic ulceration. 9.Anatomical deformation of the penis or penile implants. 10.Predisposing priapism, sickle cell anaemia, thrombocythaemia, polycythaemia, prone to venous thrombosis, hyperviscosity syndrome. 11.Known hereditary degenerative retinal disorders, including retinitis pigmentosa. 12.Previous episode of NAION. 13.Renal failure (GFR 170/100 mm Hg). 20.Bacterial infection (CRP > 2 x ULN, positive blood, urine or ascites cultures; or ascites with leucocytes = 500/µl or PMN = 250/µl) within 2 weeks prior to Baseline visit. 21.Change of regular medication and/or dosage change of drugs that may have an effect on splanchnic haemodynamics/portal pressure, e.g. ß-blockers, clonidine, prazosin, and any other antihypertensive treatment within 2 weeks prior to Baseline visit (Exception: losartan within 4 weeks prior to Baseline visit). 22.Concomitant treatment with NO-donors as nitrates, molsidomine or ß-blockers. 23.Concomitant treatment with vasopressin or somatostatin and their derivatives and analogues. 24.Concomitant treatment with platelet aggregation inhibitors, e.g. aspirin or anticoagulant, e.g. heparin. 25.Concomitant treatment with other PDE-5 inhibitors, e.g. sildenafil, tadalafil or vardenafil. 26.Treatment with ketoconazole or other CYP3A inhibitors or inducers, consumption of grapefruit juice within one week prior to Baseline visit 27.Active hepatocellular cancer or a history of hepatocellular cancer (to be excluded by ultrasound and tumour markers). 28.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. 29.Severe co-morbidity substantially reducing life expectancy. 30.Known intolerance/hypersensitivity/resistance to study drug or drugs of similar chemical structure or pharmacological profile. 31.Hypersensitivity to indocyanine green or sodium iodide, allergy to iodine, manifest hyperthyroidism, autonomous thyroid adenoma, focally or diffuse autonomies of thyroid gland. 32.Doubt about the patient’s cooperation, e.g. because of addiction to alcohol or drugs. 33.Existing or intended pregnancy or breast-feeding. 34.Participation in another clinical study within the last 30 days, simultaneous participation in another clinical study, or previous participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the change in portal blood flow by ultrasonography in patients with portal hypertension.;Secondary Objective: Change of hepatic blood flow measured by ICG-Clearance after single study drug administration. Change of time interval of ultrasound contrast media appearing in a liver vein after i.v. injection.;Primary end point(s): Change of portal flow measured by change in following haemodynamic parameter (Doppler ultrasonography): -Flow volume in the portal vein after single study drug administration ;Timepoint(s) of evaluation of this end point: First and second study day. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: First and second study day.;Secondary end point(s): •Change of portal flow measured by changes in following haemodynamic parameters (Doppler ultrasonography): -Maximal and time-averaged mean blood velocity in portal vein -Diameter of the portal vein -Resistivity indices in the common hepatic artery, splenic artery, celiac trunk and superior mesenteric artery -Time span of ultrasound contrast media appearance after injection into a cubital vein •Change of hepatic blood flow measured by ICG-Clearance after single study drug or placebo administration •Effect on systemic blood circulation | — |
Countries
Germany
Contacts
Public ContactCRO
AKP GmbH
Outcome results
None listed