Rifaximin Predicts the Complications of Decompensated Cirrhosis
Primary Purpose
Cirrhosis
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
rifaximin
Sponsored by
About this trial
This is an interventional prevention trial for Cirrhosis focused on measuring rifaximin, endotoxemia, cirrhosis, advanced cirrhosis
Eligibility Criteria
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.
Sites / Locations
- Shanghai changzheng HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
No Intervention
Arm Label
high dose of rifaximin
low dose of rifaximin
control
Arm Description
rifaximin 600 mg, bid, orally, 2 weeks and conventional treatment
rifaximin 400 mg bid,orally, 2 weeks
conventional treatment
Outcomes
Primary Outcome Measures
Serum endotoxin level
Hydrogen breath test
Fecal flora
Secondary Outcome Measures
Liver biochemistry tests
Numbers of complications of cirrhosis
Serum levels of inflammatory factors
Full Information
NCT ID
NCT02074280
First Posted
February 15, 2014
Last Updated
February 26, 2014
Sponsor
Shanghai Changzheng Hospital
1. Study Identification
Unique Protocol Identification Number
NCT02074280
Brief Title
Rifaximin Predicts the Complications of Decompensated Cirrhosis
Official Title
Rifaximin Predicts the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial
Study Type
Interventional
2. Study Status
Record Verification Date
February 2014
Overall Recruitment Status
Unknown status
Study Start Date
October 2013 (undefined)
Primary Completion Date
June 2014 (Anticipated)
Study Completion Date
December 2014 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Shanghai Changzheng Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis
Keywords
rifaximin, endotoxemia, cirrhosis, advanced cirrhosis
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
250 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
high dose of rifaximin
Arm Type
Experimental
Arm Description
rifaximin 600 mg, bid, orally, 2 weeks and conventional treatment
Arm Title
low dose of rifaximin
Arm Type
Experimental
Arm Description
rifaximin 400 mg bid,orally, 2 weeks
Arm Title
control
Arm Type
No Intervention
Arm Description
conventional treatment
Intervention Type
Drug
Intervention Name(s)
rifaximin
Intervention Description
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.
Primary Outcome Measure Information:
Title
Serum endotoxin level
Time Frame
4 weeks
Title
Hydrogen breath test
Time Frame
4 weeks
Title
Fecal flora
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Liver biochemistry tests
Time Frame
4 weeks
Title
Numbers of complications of cirrhosis
Time Frame
4 weeks
Title
Serum levels of inflammatory factors
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wei-Fen Xie, MD
Phone
86-21-81885346
Email
coss2008@yeah.net
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wei-Fen Xie, MD
Organizational Affiliation
Department of Gastroenterology, Changzheng Hospital, Second Military Medical University Shanghai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai changzheng Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200003
Country
China
Individual Site Status
Recruiting
12. IPD Sharing Statement
Citations:
PubMed Identifier
24365449
Citation
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.
Results Reference
background
PubMed Identifier
24161699
Citation
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.
Results Reference
background
PubMed Identifier
23526308
Citation
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.
Results Reference
background
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Rifaximin Predicts the Complications of Decompensated Cirrhosis
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