Clinical trial NCT02074280: Rifaximin Predicts the Complications of Decompensated Cirrhosis
Official title: Rifaximin Predicts the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cirrhosis
Keywords: rifaximin
endotoxemia
cirrhosis
advanced cirrhosis
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2014-02-28
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Serum endotoxin level
timeFrame: 4 weeks
measure: Hydrogen breath test
timeFrame: 4 weeks
measure: Fecal flora
timeFrame: 4 weeks
Secondary outcomes:
measure: Liver biochemistry tests
timeFrame: 4 weeks
measure: Numbers of complications of cirrhosis
timeFrame: 4 weeks
measure: Serum levels of inflammatory factors
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai changzheng Hospital
state: Shanghai
Study officials:
affiliation: Department of Gastroenterology, Changzheng Hospital, Second Military Medical University Shanghai
name: Wei-Fen Xie, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.