Cirrhosis, portal hypertension. Levercirrose, portale hypertensie.
Conditions
Interventions
This study consists of three interventions per patient. Patients will receive a single oral administration of a drug cocktail two weeks before TIPS placement, a day after
TIPS placement, and twelve we
Sponsors
Academic Medical Center (AMC), Amsterdam
Eligibility
Inclusion criteria
Inclusion criteria: - Liver cirrhosis as documented by liver biopsy or elastography (e.g. Fibroscan > 15 kPa) in combination with usual radiological and biochemical signs. - Age > 18 years. - Elective indication for TIPS (recurrent tense ascites, recurrent/refractory hepatic hydrothorax, or (recurrent) oesophageal or gastric bleeding treated with endoscopic band ligation (EBL) or endoscopic injection sclerotherapy (EIS) more than 2 weeks prior to screening. - Signed informed consent
Exclusion criteria
Exclusion criteria: - Age > 75 years. - History of grade III or IV HE or chronic overt HE. - Patients with (recurrent) oesophageal or gastric bleeding treated with endoscopic band ligation (EBL) or endoscopic injection sclerotherapy (EIS) within 2 weeks previous to screening. - Patients who meet the criteria for emergency TIPS for uncontrolled bleeding. - Spontaneous Bacterial Peritonitis (SBP) during the past 7 days. - Child Pugh score ≥ 10. - MELD score > 20. - Serum bilirubin 51 > μmol/L. - INR > 1.7. - Serum creatinine > 185 μmol/L. - Complete portal vein thrombosis. - Hepatocellular Carcinoma - Polycystic liver disease/ multiple large liver cysts. - Concomitant active infection. - Congestive heart failure. - Pulmonary hypertension - Bile duct obstruction with dilatation of the bile ducts. - Overt neurologic diseases such as Alzheimer’s disease, Parkinson’s disease. - Pregnant or breastfeeding women. - Drug abuse or alcoholism (>3 units of alcohol per day). - Use of alcohol for at least 3 days prior to each study day. - Strenuous exercise for at least 3 days prior to each study day, defined as more than 1 hour of exercise per day. - Use of prescription or non-prescription drugs and herbal or dietary supplements within 14 days prior to the first administration of the drug cocktail, that will not be taken after TIPS placement. - Use of tobacco products (induction liver enzymes). - Drinking of coffee/thee or caffeine containing beverages (caffeine) within 1 day prior to study (based on the half-life of caffeine: t1/2=5 hours). - Eating/drinking of grapefruit and grapefruit-containing products or star fruit for at least 2 days prior to each study day. - Allergy for the study medications
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. To assess the effect of TIPS placement on drug metabolism of different drugs, metabolized by different metabolic pathways in patients with cirrhosis using the drug cocktail approach after oral administration. Drug exposure is quantified by assessment of the area under the plasma concentration versus time curve (AUC) for each drug. | — |
Secondary
| Measure | Time frame |
|---|---|
| 2. To assess the effect of TIPS placement on pharmacokinetic parameters as clearance, volume of distribution, absorption rate, mean residence time and elimination half-life. 3. To assess the effect of TIPS placement on the postprandial bile acid, glucose, lipid and energy metabolism. | — |
Contacts
Public ContactK de Wit
Academic Medical Center (AMC), Amsterdam
Outcome results
None listed