E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Liver cirrhosis of any etilogy, complicated by decompensation and classified as Child-Pugh B or C |
Lever cirrose med ascites og dekompensation, Child-Pugh B eller C |
|
E.1.1.1 | Medical condition in easily understood language |
Liver disease |
Skrumpe lever |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024667 |
E.1.2 | Term | Liver cirrhosis |
E.1.2 | System Organ Class | 100000004871 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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, |
|
E.2.2 | Secondary objectives of the trial |
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).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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.
|
|
E.4 | Principal 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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
20 % decrease in portal pressure, measured as the hepatic venous pressure gradient (HVPG). 20 % increase in glomerular filtration rate.
|
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
For all end points end of trial |
|
E.5.2 | 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.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all endpoints end of trial |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To assess the patho physiological effects of rifaximin (Xifaxan) on haemodynamics in the cirrhotic patient. |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
One month after last visit of last subject. The trial includes a follow-up period regarding complications, mortality and morbidity, until death or end of trial. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |