Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a transjugular intrahepatic portosystemic shunt: a multi-centre randomized, double blind, placebo controlled trial. The PEARL trial
- Conditions
- hepatische encefalopathiehepatic encephalopathyneurocognitive impairment
- Registration Number
- NL-OMON55418
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 185
1. Elective TIPS placement for refractory ascites or recurrent variceal
bleeding:
* Recurrent tense ascites and one or more of the following criteria:
i. Not responding to the maximal dose of diuretics (400mg spironolactone and
160mg furosemide).
ii. Kidney insufficiency (Creatinine > 135 umol/L) induced by diuretics.
iii. Electrolyte disturbances (Sodium < 125 mmol/L, Potassium > 5.5 mmol/L)
induced by diuretics.
iv. Not tolerating higher dose of diuretics. (e.g. because of subjective side
effects like muscle cramps).
* (Recurrent) variceal bleeding, not responsive to treatment with endoscopic
band ligation and/or beta-blockers, with a high risk of failure of endoscopic
treatment:
i. Patients with a variceal bleeding and Child-Pugh C (10-13 points) cirrhosis
ii. Patients with a variceal bleeding, Child-Pugh B and an active bleeding
during endoscopy
2. Age * 18 years
3. Confirmed liver cirrhosis as documented by liver biopsy, elastography (e.g.
Fibroscan) or combination of usual radiological and biochemical criteria.
4. Signed informed consent
1. Any absolute contraindications for TIPS placement:
a. History of hepatic encephalopathy grade II-IV without precipitating factor
b. Heart failure NYHA * grade 3
c. Hepatocellular carcinoma (multifocal or large or centrally located)
d. Systemic infection / sepsis
e. Severe pulmonary hypertension
f. Unrelieved bile duct obstruction
g. Technically not feasible
h. Poor liver function (MELD score > 20)
2. Use of ciclosporin
3. Life-threating variceal bleeding with emergency TIPS placement
4. Age > 80 years
5. Non-cirrhotic portal hypertension
6. Portal vein thrombosis (main trunk)
7. Current or recent (<3 months) use of rifaximin
8. Overt neurologic diseases such as Alzheimer*s disease, Parkinson*s disease
9. Pregnant or breastfeeding women
10. Patients refusing or unable to sign informed consent
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoint is the development of OHE within three months after TIPS<br /><br>placement determined by the West Haven criteria.<br /><br><br /><br>substudy 1:<br /><br>Primary objective of this ancillary study is to assess the effect of TIPS<br /><br>placement on microbiota-host interaction based on the following assessments at<br /><br>screening, day of TIPS placement, month 3 (end of study medication treatment)<br /><br>and month 12:<br /><br>- 16s rRNA based analysis of microbiota in stool<br /><br>- 16s rRNA based analysis of microbiota in saliva<br /><br>- Circulating biomarkers for inflammatory, circulatory and endothelial function.<br /><br><br /><br>substudy 2:<br /><br>- To compare the activation status, immunological and metabolic function<br /><br>of circulating monocytes/macrophages obtained from patients with alcoholic<br /><br>liver cirrhosis (ALD).</p><br>
- Secondary Outcome Measures
Name Time Method