Rifaximin Predicts the Complications of Decompensated Cirrhosis

Cirrhosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02074280
• Other study ID #: LPDLCC-1
• Status: Recruiting
• Phase: Phase 4
• First received: February 15, 2014
• Last updated: February 26, 2014
• Start date: October 2013
• Est. completion date: December 2014

Study information

• Verified date: February 2014
• Source: Shanghai Changzheng Hospital
• Contact: Wei-Fen Xie, MD
• Phone: 86-21-81885346
• Email: coss2008[@]yeah.net
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: December 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cirrhosis
• Liver Cirrhosis

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
China	Shanghai changzheng Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Changzheng Hospital

Country where clinical trial is conducted

China, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum endotoxin level		4 weeks	No
Primary	Hydrogen breath test		4 weeks	No
Primary	Fecal flora		4 weeks	No
Secondary	Liver biochemistry tests		4 weeks	No
Secondary	Numbers of complications of cirrhosis		4 weeks	No
Secondary	Serum levels of inflammatory factors		4 weeks	No