Clinical trial NCT02190357: Rifaximin Reduces the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial
Official title: Rifaximin Reduces the Complications of Decompensated Cirrhosis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Cirrhosis
Keywords: Cirrhosis
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
First posted: 2014-07-15
Enrollment: 200
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: TREATMENT

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 effect of rifaximin on 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 effect of rifaximin on the complications of advanced cirrhosis.

Eligibility criteria: 1. Eligicility criteria (1) Willing to give written informed consent and comply with the study restrictions and requirements (2) Age from 18 to 75 years at screening (3) Clinical diagnosis of decompensated liver cirrhosis
2. Exclusion criteria (1) Episodes of overt hepatic encephalopathy (HE), esophageal gastric variceal bleeding (EGVB) or spontaneous bacterial peritonitis (SBP) within one month (2) Hepatitis B Virus (HBV) DNA ≥ 500 copy/ml (3) Standard antiviral treament duration less than six months for patients receiving antiviral treatment for hepatitis B or hepatitis C (4) Planned to receive or change the antiviral treament projects at the screening (5) Unwilling to stop alcohol abuse after inclusion (≥20 g/ d for women or ≥40 g/d for men) (6) Serum total bilirubin ≥ 170 μmol/L (7) Serum sodium level \< 125 mmol/L (8) White blood cell count \< 1×109/L (9) Serum creatinine ≥ 1.2 fold of upper limits of normal (10) Clinically diagnosed or suspected as liver malignancy (11) Previous use of antibiotics within two weeks before inclusion (12) HIV seropositivity (13) Poorly controlled hypertension, diabetes mellitus or other severe heart and lung diseases (14) Known hypersensitivity to rifaximin (15) Pregnancy and lactation woman (16) Participated in other studies within three months before screening (17) Not suitble for participating the study judged by investigators

Primary outcomes:
measure: number of death
timeFrame: 6 months
measure: numbers of liver transplantation
timeFrame: 6 months
measure: numbers of hepatic encephalopathy
timeFrame: 6 months
measure: Numbers of other complications of cirrhosis
timeFrame: 6 months
Secondary outcomes:
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.
citation: Zeng X, Sheng X, Wang PQ, Xin HG, Guo YB, Lin Y, Zhong JW, He CZ, Yin J, Liu TT, Ma WJ, Xiao X, Shi PM, Yuan ZL, Yang L, Ma X, Xu JM, Shen XZ, Yang CQ, Zhu X, Lv NH, Xie WF. Low-dose rifaximin prevents complications and improves survival in patients with decompensated liver cirrhosis. Hepatol Int. 2021 Feb;15(1):155-165. doi: 10.1007/s12072-020-10117-y. Epub 2021 Jan 1.