Liver cirrhosis of any etilogy, complicated by decompensation and classified as Child-Pugh B or C MedDRA version: 17.1 Level: LLT Classification code 10024667 Term: Liver cirrhosis System Organ Class: 100000004871
Conditions
Interventions
Trade Name: Xifaxan
Pharmaceutical Form: Tablet
INN or Proposed INN: RIFAXIMIN
CAS Number: 80621-81-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 550-
Pharmaceu
Sponsors
Flemming Bendtsen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patients with decompensated liver cirrhosis and clinical signs of ascites, verified by ultrasonography or CT scan within the last three months. - Age between 18 and 80 years. - Portal hypertension and a hepatic venous pressure gradient (HVPG) of 10 mmHg or more. - Women of child-bearing age should use safe anti conception, defined as either hormonal anti conception or intrauterine device. 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 40 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 17
Exclusion criteria
Exclusion criteria: - Child-Pugh Score above 13 - Clinical signs of infection evaluated by blood biochemistry, urine culture and if applicable ascites puncture, and through clinical assessment by the investigator. - Received antibiotic treatment within 14 days prior to inclusion - Presence of hepatocellular carcinoma. - Ongoing invasive cancer or invasive cancer within the last five years, - Overt hepatic encephalopathy (HE above grade 1), - Serum creatinine > 200 mmol/l, - Transfusion requiring bleeding within one week prior to inclusion, - S-hemoglobin levels of < 5,5 mmol/L - Severe cardiac, pulmonary or kidney diseases or Type 1 diabetes mellitus, - Continuous alcohol abuse with symptoms of abstinence - Expected survival less than 3 months, - Denied consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): 20 % decrease in portal pressure, measured as the hepatic venous pressure gradient (HVPG). 20 % increase in glomerular filtration rate. ;Timepoint(s) of evaluation of this end point: For all end points end of trial ;Main Objective: This randomized clinical trial will be assessing the effect of rifaximin on pathophysiology and haemodynamics in the patient with decompensated liver cirrhosis, and addressing the effect of rifaximin on several organs on marker level. We hypothesize that intestinal decontamination with rifaximin in patients with cirrhosis and ascites will interrupt bacterial translocation, diminish the following inflammatory response, prevent splanchnic vasodilatation and portal systemic contraction and thereby reduce the risk clinical complications to cirrhosis. Hence, rifaximin: Will decrease portal pressure, measured as the hepatic venous pressure gradient (HVPG). Will improve renal function expressed as an increase in glomerular filtration rate, ;Secondary Objective: To assess if intestinal decontamination with rifaximin : - Will ameliorate the peripheral and splanchnic vasodilatation by a decrease in cardiac output (CO) and an increase in arterial blood pressure and systemic vascular resistance (SVR). These effects should also be reflected by a trend towards normalization of vasoactive hormones. - Will down regulate markers of inflammation expressed as a decrease in proinflammatory cytokines (i.e. TNF-a and interleukines) and high sensitivity CRP. - Attenuate markers of infection, expressed by bacterial DNA and lipopolysaccharide binding protein (LPS-BP). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 20 % decrease in cardiac output 10 % increase in arterial blood pressure and systemic vascular resistance (SVR). Normalization of vasoactive hormones. 20 % down regulation of markers of inflammation. Attenuation of markers of infection. Depletion of bacterial overgrowth. ;Timepoint(s) of evaluation of this end point: For all endpoints end of trial | — |
Countries
Denmark
Contacts
Public ContactDepartment of Gastroenterology
Copenhagen University Hospital Hvidovre
Outcome results
None listed