Cirrhosis
Conditions
Keywords
rifaximin, endotoxemia, cirrhosis, advanced cirrhosis
Brief summary
Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and increased intestinal permeability all leading to an increase in bacterial translocation and increased endotoxemia. Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract. It has been suggested that oral prophylactic antibiotics or bowel decontamination might improve long-term outcomes in patients with cirrhosis. The aim of this study was to explore the suitable dose of rifaximin to alleviate endotoxemia and prevent the complications of advanced cirrhosis.
Detailed description
Cirrhotic patients are predisposed to intestinal dysmotility, bacterial overgrowth, and increased intestinal permeability all leading to an increase in bacterial translocation and increased endotoxemia. Cirrhotics with bacterial translocation and endotoxemia manifest hemodynamic derangement with lower systemic vascular resistance, higher cardiac output, and lower mean arterial pressure. Moreover, endotoxins may increase portal pressure by increasing vascular resistance which may be promoted through the cytokine-stimulated intrahepatic release of endothelin and cyclo-oxygenase products. Indeed, bacterial infections are common in cirrhotic patients and have approximately 30% mortality at one month and a further 30% mortality at 12 months as documented in a systematic review comprising almost 12 000 patients. It follows that altering gut flora to decrease endotoxin levels may lead to improved prognosis in cirrhosis. Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract. It has been suggested that oral prophylactic antibiotics or bowel decontamination might improve long-term outcomes in patients with cirrhosis, not only by reducing the risk of infections but also by reducing hepatic vein pressure gradient (HVPG). The aim of this study was to explore the suitable dose of rifaximin to alleviate endotoxemia and prevent the complications of advanced cirrhosis.
Interventions
DRUGrifaximin
Rifaximin is an antibiotic that is virtually non-absorbed after oral administration and exhibits broad spectrum antimicrobial activity against both aerobic and anaerobic gram-positive and gram-negative microorganisms within the gastrointestinal tract.
Sponsors
Shanghai Changzheng Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Decompensated cirrhosis * Child-Pugh B or C stage
Exclusion criteria
* severe complications of cirrhosis in the past one month. * renal dysfunction. * administration of antibiotics in the past two weeks. * malignant tumors. * HIV infection. * severe heart and lung disease * sensitivity to rifaximin * Pregnancy and lactation woman * Patients who have took part in other clinical trials in the past three months.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Serum endotoxin level | 4 weeks |
| Hydrogen breath test | 4 weeks |
| Fecal flora | 4 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Liver biochemistry tests | 4 weeks |
| Numbers of complications of cirrhosis | 4 weeks |
| Serum levels of inflammatory factors | 4 weeks |
Countries
China
Contacts
Primary ContactWei-Fen Xie, MD
Outcome results
None listed