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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| high dose of rifaximin | Experimental | rifaximin 600 mg, bid, orally, 2 weeks and conventional treatment |
|
| low dose of rifaximin | Experimental | rifaximin 400 mg bid,orally, 2 weeks |
|
| control | No Intervention | conventional treatment |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rifaximin | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum endotoxin level | 4 weeks | |
| Hydrogen breath test | 4 weeks | |
| Fecal flora | 4 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Liver biochemistry tests | 4 weeks | |
| Numbers of complications of cirrhosis | 4 weeks | |
| Serum levels of inflammatory factors |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Wei-Fen Xie, MD | Contact | 86-21-81885346 | coss2008@yeah.net |
| Name | Affiliation | Role |
|---|---|---|
| Wei-Fen Xie, MD | Department of Gastroenterology, Changzheng Hospital, Second Military Medical University Shanghai | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai changzheng Hospital | Recruiting | Shanghai | Shanghai Municipality | 200003 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24365449 | Background | Mullen KD, Sanyal AJ, Bass NM, Poordad FF, Sheikh MY, Frederick RT, Bortey E, Forbes WP. Rifaximin is safe and well tolerated for long-term maintenance of remission from overt hepatic encephalopathy. Clin Gastroenterol Hepatol. 2014 Aug;12(8):1390-7.e2. doi: 10.1016/j.cgh.2013.12.021. Epub 2013 Dec 21. | |
| 24161699 | Background |
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| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D019446 | Endotoxemia |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D016470 | Bacteremia |
| D018805 | Sepsis |
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| ID | Term |
|---|---|
| D000078262 | Rifaximin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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| 4 weeks |
| Xu D, Gao J, Gillilland M 3rd, Wu X, Song I, Kao JY, Owyang C. Rifaximin alters intestinal bacteria and prevents stress-induced gut inflammation and visceral hyperalgesia in rats. Gastroenterology. 2014 Feb;146(2):484-96.e4. doi: 10.1053/j.gastro.2013.10.026. Epub 2013 Oct 22. |
| 23526308 | Background | Lutz P, Parcina M, Bekeredjian-Ding I, Hoerauf A, Strassburg CP, Spengler U. Spontaneous bacterial peritonitis by Pasteurella multocida under treatment with rifaximin. Infection. 2014 Feb;42(1):175-7. doi: 10.1007/s15010-013-0449-4. Epub 2013 Mar 25. |
| D007239 |
| Infections |
| D014115 | Toxemia |
| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |