Track topics on Twitter Track topics that are important to you
The study will be conducted in two phases. Phase A will evaluate the contribution of bacterial overgrowth and colonic inertia to development of Hepatic Encephalopathy (HE)in 50 ambulatory subjects with HE and hepatitis C cirrhosis. This phase will include a Screening and Evaluation Visit.
Phase B will evaluate the effect of rifaximin on bacterial outgrowth and severity of HE in 20 of the subjects enrolled in Phase A who have a somewhat greater degree of encephalopathy.
The purpose of this study is to evaluate the following:
1. the relationship between bacterial overgrowth and the presence and severity of HE in patients with hepatitis C cirrhosis;
2. the effectiveness and tolerability of rifaximin relative to placebo in treatment of HE associated with hepatitis C cirrhosis;
3. the relationship between bacterial overgrowth and the presence and severity of HE before and after rifaximin treatment.
Hepatic encephalopathy is a frequent and occasionally refractory complication of cirrhosis and is associated with impaired quality of life. Its severity may not correlate with other parameters of liver dysfunction. Although multiple pathogenic mechanisms for the condition have been proposed, most include the participation of bacterial toxins, especially ammonia, produced in the gastrointestinal tract. Treatment options for hepatic encephalopathy at this time are limited to lactulose and neomycin. Lactulose is frequently poorly tolerated, and many patients are non-compliant with its use. In patients with renal insufficiency in whom hepatic encephalopathy is frequently problematic, use of neomycin is contraindicated due to ototoxicity and nephrotoxicity.
Autonomic dysfunction is common in patients with cirrhosis and could contribute to the development of hepatic encephalopathy by impairment of intestinal motility, leading to bacterial overgrowth and colonic inertia.
The following questions will be addressed:
A. Is impaired intestinal transit and bacterial overgrowth associated with the presence and severity of hepatic encephalopathy?
50 patients will undergo a detailed clinical evaluation for severity of liver disease, hepatic encephalopathy and assessment of intestinal transit and bacterial overgrowth with radiographic marker study and breath test analysis. Multivariate analysis will then be performed to determine the relationship of intestinal transit and evidence of bacterial overgrowth with the presence and severity of hepatic encephalopathy.
B. Does treatment with rifaximin improve bacterial overgrowth and hepatic encephalopathy?
20 patients from the above population with significant encephalopathy will be randomized to receive either rifaximin or placebo. Post-treatment evaluation for severity of hepatic encephalopathy and breath test analysis for bacterial overgrowth will then be performed. The effect of treatment on changes in hepatic encephalopathy and bacterial overgrowth and the relationship between changes in bacterial overgrowth and severity of hepatic encephalopathy will also be assessed.
Phase A Endpoints: Degree of bacterial overgrowth and its correlation with the grade of hepatic encephalopathy (if present).
Phase B Endpoints: To demonstrate improvement in degree of HE with treatment of Rifaximin
Efficacy Endpoints The primary efficacy endpoint for Phase B of the study will be the change from baseline in the proportion of patients with no HE, minimal HE (no symptoms, abnormal psychometric testing), mild persistent HE (mild symptoms), and persistent Stage II HE (presence of asterixis, history of hospitalization for spontaneous Stage III or IV HE).
Secondary efficacy endpoints for Phase B will be the following:
To demonstrate improvement in intestinal transit time for patients (based on Lactulose Hydrogen Breath Test) To demonstrate improvement in bacterial overgrowth, improved insomnia, flatulence, and quality of life.
To demonstrate that rifaximin improved patients' symptoms of insomnia, flatulence, and quality of life measure with the degree of bacterial overload and the impaired intestinal transit time.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
New York Presbyterian Hospital: Weill Medical College of Cornell University
Weill Medical College of Cornell University
Published on BioPortfolio: 2014-07-24T14:25:51-0400
Several studies have been showed that rifaximin can improve cognitive functions, driving simulator performance and health-related quality of life in patients with minimal hepatic encephalo...
The purpose of this study is to determine whether alteration of gut flora with rifaximin can lead to improvement in driving performance, psychometric test performance, and quality of life ...
This study evaluates hepatic encephalopathy (HE) and liver-related hospitalization rates and duration of stay in patients with HE treated with rifaximin-α 550mg compared to patients rece...
The purpose of this study is to determine if the study drug is safe and effective in preventing Hepatic Encephalopathy (HE).
Rifaximin therapy will improve brain functioning on MRI scanning.
Many regimens are tried in managing overt hepatic encephalopathy (HE). We investigated the efficacy of rifaximin versus metronidazole in management of an acute episode of HE on top of cirrhosis.
Rifaximin-α 550 mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt HE (OHE) and the risk of HE-related hospitalisations compared with lactulose alon...
Hepatic encephalopathy is a serious neurologic complication of acute and chronic liver diseases. We previously showed that aberrant bile acid signaling contributes to the development of hepatic enceph...
The evaluation to determine the cause of hepatic encephalopathy consists primarily of laboratory testing to rule out infections and metabolic causes. Despite lack of evidence, it is a common practice ...
Serum electrolyte derangements are common in patients with decompensated cirrhosis hospitalized for hepatic encephalopathy. There are limited data describing the association between electrolyte levels...
A synthetic disaccharide used in the treatment of constipation and hepatic encephalopathy. It has also been used in the diagnosis of gastrointestinal disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p887)
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.
A transmissible spongiform encephalopathy of cattle associated with abnormal prion proteins in the brain. Affected animals develop excitability and salivation followed by ATAXIA. This disorder has been associated with consumption of SCRAPIE infected ruminant derived protein. This condition may be transmitted to humans, where it is referred to as variant or new variant CREUTZFELDT-JAKOB SYNDROME. (Vet Rec 1998 Jul 25;143(41):101-5)
A drug-metabolizing enzyme of the hepatic microsomal oxidase system which catalyzes the oxidation of the N-methyl group of ethylmorphine with the formation of formaldehyde.
Cholangiocarcinoma arising near or at the confluence of the right and left hepatic ducts (COMMON HEPATIC DUCT). These tumors are generally small, sharply localized, and seldom metastasizing.
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...
Astroesophageal Reflux Disease (GERD) Barrett's Esophagus Celiac Disease Cholesterol Crohn's Disease Gastroenterology Hepatitis Hepatology Irritable Bowel Syndrome (IBS) Pancreatitis Peptic Ulcer Disease...