Administration of Rifaximin to Improve Liver Regeneration and Outcome Following Major Liver Resection

NCT02555293 | Terminated Phase 2

• 1 other identifier: CTC-A 13-129
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

Surgery is in almost all cases the only potentially curative treatment option for patients with primary or secondary malignancies of the liver. However, in most cases oncological resections ("R0-resections") can only be achieved by performing major liver resections (4 or more liver segments), which is related to considerable postoperative complications such as systemic infections and postoperative liver insufficiency (postresectional liver failure (PRLF)). Despite optimized preoperative and postoperative strategies of care presently, up to 32-55% of patients display severs postoperative complications (Clavien score ≥ 3a) and 5% even suffer from a severe PRLF. Recent observations in murine disease models as well as human patients suggested that postoperative alterations of hemodynamics within the portal vein tract as well as postoperative modulations of the immune response facilitates the translocation of gut bacteria in the blood, leading to systemic infections and sepsis. Moreover it became apparent that inflammatory mediators, released by the gut microbiota might negatively affect postoperative liver regeneration. Rifaximin (Xifaxan®) is a novel and potent, semisynthetic antibiotic that efficiently acts against most enteric bacteria and significantly reduced liver inflammation and liver fibrosis in animal studies. Moreover, Rifaximin is very well tolerated, even in patients with liver insufficiency.

Conditions

Malignant Liver Disease; Major Liver Resection

Keywords

Liver resection; fibrosis; inflammation; Rifaximin

Outcome Measures

Primary Outcomes (1)

• Effect of Rifaximin on postoperative liver function

  LiMAx liver function percentage increase on postoperative day 7 in relation to LiMAx value on postoperative day 4 compared to a control group without Rifaximin treatment. LiMAx will be made after at least 14 days but up to 28 days of treatment (control group analogue) dependent on the need for a PVE and the period between PVE or randomization and surgery

  Postoperative day 7 in relation to postoperative day 4

Secondary Outcomes (4)

• postoperative morbidity/Complications

  minimum 14 days after liver resection

• Liver volume percentage increase

  14 up to 21 days before liver resection at baseline and 7 days after the operation

• liver function percentage increase

  14 up to 21 days before liver resection at baseline (all), on preoperative day 1 (PVE group only) and on postoperative day 4 and day 7 (all)

• Time to functional recovery

  minimum 14 days starting on operation day

Study Arms (2)

film-coated Rifaximin (550 mg)

EXPERIMENTAL

(550 mg) tablet twice daily for at least 14 days but up to 28 days dependent on the need for a PVE and the period between PVE (portal vein embolization) or randomization and surgery. Preoperative Rifaximin treatment in case of a PVE will start the day after PVE and will last for 14-21 days. In case patients are not pre-treated with a PVE they will receive Rifaximin for 7-10 days prior to surgery. Regardless of PVE, patients will receive additional Rifaximin treatment the first 7 days postoperatively.

Drug: XIFAXAN® (Rifaximin)

standard therapy

NO INTERVENTION

Patients directed to the control group will not receive Rifaximin.

Interventions

XIFAXAN® (Rifaximin) DRUG

Also known as: NDA 22-554

film-coated Rifaximin (550 mg)

Eligibility Criteria

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

You may qualify if:

• Patients undergoing a liver resection of at least 4 segments
• Age \> 18 years \< 80 years
• BMI 18-40
• Patients with ASA (American Society of Anesthesiologists) I-III
• Written informed consent prior to study participation

You may not qualify if:

• Patients with ASA IV-V
• Contraindication for MRI (see 5.4.3)
• Underlying chronic liver disease such as severe fibrosis or liver cirrhosis
• Need for procedures additive to partial liver resection
• Participation in other liver related trials
• BMI \> 40
• Previous liver transplantation or porto-systemic shunt
• Concomitant acute infectious diseases
• Renal insufficiency
• Hypersensitivity to Rifaximin
• Concomitant HIPEC (hypertherme intraperitoneale chemoperfusion) treatment
• ALPPS (associating liver partition and portal vein ligation for staged hepatectomy)
• Pregnant females as determined by positive \[serum or urine\] hCG (human chorionic gonadotropin) test at Screening or prior to dosing. Participants of child-bearing age should use adequate contraception as defined in the study protocol.
• Lactating females
• The subject has a history of any other illness, which, in the opinion of the investigator, might pose an unacceptable risk by administering study medication.

Sponsors & Collaborators

• RWTH Aachen University: lead

Study Sites (1)

RWTH Aachen University

Aachen, 52074, Germany

Location

Related Publications (1)

• Bednarsch J, Czigany Z, Loosen SH, Heij L, Ruckgaber L, Maes H, Krause JP, Reen M, Toteva B, Vosdellen T, Bruners P, Lang SA, Ulmer TF, Roderburg C, Luedde T, Neumann UP. Perioperative rifaximin is not associated with enhanced functional and volumetric recovery after major liver resection. Sci Rep. 2021 Sep 9;11(1):17936. doi: 10.1038/s41598-021-97442-w.

  PMID: 34504196 DERIVED

MeSH Terms

Conditions

Fibrosis; Inflammation

Interventions

Rifaximin

Condition Hierarchy (Ancestors)

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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2015
• First Posted: September 21, 2015
• Study Start: February 1, 2016
• Primary Completion: November 20, 2020
• Study Completion: November 20, 2020
• Last Updated: November 1, 2021

Record last verified: 2020-10

Locations

DE (1)