A Phase 4 interventional study of Rifaximin 550 milligram Oral Tablet [XIFAXAN] and Placebo oral tablet in Hepatic Encephalopathy, Cirrhosis, Liver and Portal Hypertension, sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). Recruiting at 6 sites in 2 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-01-28.
Sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Phase 4, Interventional, and Prevention
Rationale: Hepatic encephalopathy (HE) is a major and common complication in patients with liver cirrhosis. HE can be classified in the extensive range of neurocognitive deterioration as minimal HE (MHE), covert HE (grade I), or overt HE (OHE, grade II-IV). Liver cirrhosis is the most common cause of portal hypertension (PH). Patients who develop complications of PH, like variceal bleeding or refractory ascites, can benefit from a Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement. Unfortunately, post-TIPS HE is a common and often severe complication. Incidence of new onset or worsening of HE after TIPS is approximately 20-45%. Currently there is no strategy to prevent post-TIPS HE.
Objective: To assess the incidence of post-TIPS OHE within the first three months after prophylactic administration of lactulose and rifaximin versus placebo in patients who undergo Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.
Study design: A multicentre, randomized, placebo-controlled, double blind study.
Study population: Adult consecutive patients undergoing elective TIPS placement (for refractory ascites or secondary prophylaxis in variceal bleeding) in all Dutch academic centres where TIPS procedures are performed: Amsterdam UMC, location Academic Medical Centre (AMC), Erasmus MC, Leiden University Medical Centre (LUMC), Maastricht University Medical Centre+ (MUMC+), Radboud University Medical Centre (Radboudumc), University Medical Centre Groningen (UMCG), and University Hospitals Leuven (UZ Leuven) in Belgium.
Intervention: Rifaximin 550 milligram (mg) b.i.d. will be prescribed, in combination with a starting dose of 25 milliliter (mL) lactulose b.i.d. and further dependent on the amount of daily bowel movements, with the objective not to exceed more than two soft stools per day. Intervention will start 72 hours before TIPS placement, and will last till three months after TIPS placement. The control group will receive placebo in combination with lactulose (as described above).
Main study parameters/endpoints: Primary endpoint is the development of OHE within three months after TIPS placement determined by the West Haven criteria. Secondary endpoints are 90 day mortality; development of a second episode of OHE within the first three months; development of OHE in the period between three and twelve months after TIPS placement; development of MHE between TIPS placement and twelve months after placement; the increase of the psychometric hepatic encephalopathy score (PHES) and simplified one minute animal naming test (S-ANT1) compared to baseline. Differences in molecular composition of peripheral / portal blood samples at TIPS placement. Furthermore, quality of life will be assessed.
225 studies on the registry are indexed under Hepatic Encephalopathy; 53 are open to participants now.
This study's planned enrollment of 238 is above the median of 60 across 154 interventional studies indexed under Hepatic Encephalopathy.
Browse Hepatic Encephalopathy studies →Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) is the lead sponsor of 532 studies on the registry; 183 are open to participants now.
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Elective TIPS placement for 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 (400 milligram spironolactone and 160 milligram 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 beta-blockers, with a high risk of failure of endoscopic treatment:
i. Patients with a variceal bleeding and C (10-13 points) cirrhosis or ii. Patients with a variceal bleeding, Child-Pugh B and an active bleeding during endoscopy
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Rifaximin 550 milligram b.i.d. combined with lactulose
Drug: Rifaximin 550 milligram Oral Tablet [XIFAXAN] · Drug: Lactulose 667 milligram/milliliter Oral Solution
Placebo b.i.d. combined with lactulose
Drug: Placebo oral tablet · Drug: Lactulose 667 milligram/milliliter Oral Solution
Rifaximin 550 milligram b.i.d. 72 hours before TIPS placement till 3 months post-TIPS
Also known as: TARGAXAN
Placebo b.i.d. 72 hours before TIPS placement till 3 months post-TIPS
Also known as: Placebo
Lactulose based on soft stool frequency, 72 hours before TIPS placement till 3 months post-TIPS
Also known as: Lactulose syrup
post-TIPS Hepatic Encephalopathy
post-TIPS Hepatic Encephalopathy
Time frame: First 3 months after TIPS placement
Mortality
Mortality
Time frame: 90 days
Transplant free survival
Transplant free survival
Time frame: One year
time to development of post-TIPS HE episode(s)
time to development of post-TIPS HE episode(s)
Time frame: One year
development of a second episode of post-TIPS HE
development of a second episode of post-TIPS HE
Time frame: 3 months
development of post-TIPS HE between 3-12 months after TIPS placement
development of post-TIPS HE between 3-12 months after TIPS placement
Time frame: 3-12 months
change in Psychometric Hepatic Encephalopathy Score (PHES) compared to baseline
change in total PHES score compared to baseline (range -15 - +5) a lower score is a worse outcome
Time frame: One year
change in one-minute animal naming test compared to baseline
change in one-minute animal naming test compared to baseline
Time frame: One year
differences in molecular composition of peripheral / portal blood samples
differences in molecular composition of peripheral / portal blood samples at TIPS placement
Time frame: One year
differences in molecular composition of peripheral blood samples
differences in molecular composition of peripheral blood samples at baseline, compared to day 10 post-TIPS, week 4, week 12, and week 52;
Time frame: One year
Health related Quality of life
Health related Quality of life, measured by EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) questionnaire
Time frame: One year
Disease rrelated Quality of life
Health related Quality of life, Liver Disease Symptom Index (LDSI) 2.0 questionnaire.
Time frame: One year
Cost-effectiveness
Cost-effectiveness, measured by a combined questionnaire, based on institute for Medical Technology Assessment (iMTA) Productivity Cost Questionnaire (iPCQ)/Medical Consumption Questionnaire (iMCQ)
Time frame: One year
Plan to share: No
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