Rifaximin Reduces the Complications of Decompensated Cirrhosis: a Randomized Controlled Trial

NCT ID: NCT02190357

Last Updated: 2016-09-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 200 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-08-31
• Study Completion Date: 2019-08-31

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.

Conditions

Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rifaximin

400 mg bid,orally

Group Type: EXPERIMENTAL

Rifaximin

Intervention Type: 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.

controlled group

no intervention

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Rifaximin

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Changzheng Hospital

OTHER

Sponsor Role: lead

Responsible Party

Wei-Fen Xie

Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wei-Fen Xie, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai

Locations

Shanghai changzheng Hospital

Shanghai, Shanghai Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wei-Fen Xie, MD

Role: CONTACT

coss2008@yeah.net

86-21-81885341

Facility Contacts

Xin Zeng, MD,PhD

Role: primary

zengxinmd1978@163.com

86-21-81885345

Wen-Ping Xu, MD,PhD

Role: backup

xwp198527@sina.com

86-21-81885346

References

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.

Reference Type: RESULT

PMID: 24365449 (View on PubMed)

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.

Reference Type: RESULT

PMID: 24161699 (View on PubMed)

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.

Reference Type: RESULT

PMID: 23526308 (View on PubMed)

Zacharias HD, Kamel F, Tan J, Kimer N, Gluud LL, Morgan MY. Rifaximin for prevention and treatment of hepatic encephalopathy in people with cirrhosis. Cochrane Database Syst Rev. 2023 Jul 19;7(7):CD011585. doi: 10.1002/14651858.CD011585.pub2.

Reference Type: DERIVED

PMID: 37467180 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33385299 (View on PubMed)

Other Identifiers

LPDLCC-2

Identifier Type: -

Identifier Source: org_study_id