Intestinal Decontamination With Rifaximin. The Inflammatory and Circulatory State in Patients With Cirrhosis

NCT01769040 | Completed Phase 4 DMC

• 2 other identifiers: RifaxNK1506122012-002890-71
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This investigational trial will be assessing the effect of rifaximin on pathophysiology and haemodynamics in the patient with liver cirrhosis, and addressing the effect of rifaximin on several organs on marker level. The molecular and physiological effects of rifaximin will be explored. The investigators hypothesize that intestinal decontamination with rifaximin in patients with cirrhosis and ascites will interrupt bacterial translocation from the gut, diminish the following inflammatory response, prevent splanchnic vasodilatation and portal systemic contraction and thereby reduce the risk clinical complications to cirrhosis. If rifaximin can correct small intestinal bacterial overgrowth and demonstrate improvement in liver haemodynamics, renal function and systemic dynamics, then these effects may contribute to the overall well-being of the patient and prevent complications to the underlying cirrhosis such as risk of infections, progression of disease, and admission to hospital.

Conditions

Liver Cirrhosis; Ascites

Keywords

Decompensated liver cirrhosis; Ascites; Haemodynamics; Small intestinal bacterial overgrowth; Pathophysiology

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Hepatic venous pressure gradient (HVPG)

  Evaluation of a change in HVPG where values at baseline are compared to values after treatment at 29 days.

  29 days

Secondary Outcomes (1)

• Change from baseline in Glomerular filtration rate (GFR)

  29 days

Other Outcomes (3)

• Change from baseline of inflammatory markers (TNF-alpha, interleukins, etc.)

  day 29

• Change from baseline of potential small intestinal bacterial overgrowth

  days 28-30

• six-month mortality and comorbidity

  180 days

Study Arms (2)

Rifaximin

EXPERIMENTAL

Rifaximin tablets for oral ingestion, 550 mg twice daily for 28 days.

Drug: Rifaximin

Placebo tablets

PLACEBO COMPARATOR

Placebo tablets similar in shape and size to intervention treatment, 1 tablet twice daily for 28 days.

Drug: placebo

Interventions

Rifaximin DRUG

550 mg two times daily for 28 days

Also known as: Xifaxan

Rifaximin

placebo DRUG

Placebo tablets

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Decompensated liver cirrhosis and clinical signs of ascites
• Age 18 - 80 years
• Portal hypertension and hepatic venous pressure gradient (HVPG) of 10 mmHg or more
• Women of child-bearing age must use safe anticonception, either hormonal anticonception or intrauterine device (IUD)

You may not qualify if:

• Child-Pugh score above 12
• Clinical signs of infection or biochemical signs of infection with leucocytes \> 10x10'9/L and C-Reactive Protein (CRP)\> 20 or positive urine culture
• Hepatocellular carcinoma within the last year
• Invasive cancer within the last five years
• Hepatic encephalopathy above grade 1
• serum creatinine \> 200 micromoles/L
• severe cardiac, pulmonary or kidney disease or IDDM
• alcohol abuse and symptoms of abstinences
• Expected survival less than 3 months
• Denied consent

Sponsors & Collaborators

• Copenhagen University Hospital, Hvidovre: lead
• Norgine: collaborator
• Region MidtJylland Denmark: collaborator
• Statens Serum Institut: collaborator

Study Sites (1)

Copenhagen University hospital Hvidovre

Hvidovre, 2650, Denmark

Location

Related Publications (4)

• 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.

  PMID: 37467180 DERIVED

• Kimer N, Gluud LL, Pedersen JS, Tavenier J, Moller S, Bendtsen F. The Psychometric Hepatic Encephalopathy Syndrome score does not correlate with blood ammonia, endotoxins or markers of inflammation in patients with cirrhosis. Transl Gastroenterol Hepatol. 2021 Jan 5;6:8. doi: 10.21037/tgh.2020.02.14. eCollection 2021.

  PMID: 33409402 DERIVED

• Kimer N, Pedersen JS, Tavenier J, Christensen JE, Busk TM, Hobolth L, Krag A, Al-Soud WA, Mortensen MS, Sorensen SJ, Moller S, Bendtsen F; members of the CoRif study group. Rifaximin has minor effects on bacterial composition, inflammation, and bacterial translocation in cirrhosis: A randomized trial. J Gastroenterol Hepatol. 2018 Jan;33(1):307-314. doi: 10.1111/jgh.13852.

  PMID: 28671712 DERIVED

• Kimer N, Pedersen JS, Busk TM, Gluud LL, Hobolth L, Krag A, Moller S, Bendtsen F; Copenhagen Rifaximin (CoRif) Study Group. Rifaximin has no effect on hemodynamics in decompensated cirrhosis: A randomized, double-blind, placebo-controlled trial. Hepatology. 2017 Feb;65(2):592-603. doi: 10.1002/hep.28898. Epub 2016 Dec 24.

  PMID: 27775818 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Ascites

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Nina Kimer, MD

  Department of Gastroenterology, Cpenhagen University Hospital Hvidovre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Phd-student

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 16, 2013
• Study Start: November 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 20, 2016

Record last verified: 2016-01

Locations

DK (1)