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

NCT ID: NCT02555293

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2020-11-20

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

Study Design

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

Study Groups

film-coated Rifaximin (550 mg)

(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.

Group Type: EXPERIMENTAL

XIFAXAN® (Rifaximin)

Intervention Type: DRUG

standard therapy

Patients directed to the control group will not receive Rifaximin.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

XIFAXAN® (Rifaximin)

Intervention Type: DRUG

Other Intervention Names

NDA 22-554

Eligibility Criteria

Inclusion Criteria

1. Patients undergoing a liver resection of at least 4 segments

2. Age > 18 years < 80 years

3. BMI 18-40

4. Patients with ASA (American Society of Anesthesiologists) I-III

5. Written informed consent prior to study participation

Exclusion Criteria

1. Patients with ASA IV-V

2. Contraindication for MRI (see 5.4.3)

3. Underlying chronic liver disease such as severe fibrosis or liver cirrhosis

4. Need for procedures additive to partial liver resection

5. Participation in other liver related trials

6. BMI > 40

7. Previous liver transplantation or porto-systemic shunt

8. Concomitant acute infectious diseases

9. Renal insufficiency

10. Hypersensitivity to Rifaximin

11. Concomitant HIPEC (hypertherme intraperitoneale chemoperfusion) treatment

12. ALPPS (associating liver partition and portal vein ligation for staged hepatectomy)

13. 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.

14. Lactating females

15. 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.

16. The subject received an investigational drug within 30 days prior to inclusion into this study

17. The subject has any current or past medical condition and/or required medication to treat a condition that could affect the evaluation of the study

18. The subject is unwilling or unable to follow the procedures outlined in the protocol

19. The subject is mentally or legally incapacitated

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

RWTH Aachen University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

RWTH Aachen University

Aachen, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 34504196 (View on PubMed)

Other Identifiers

CTC-A 13-129

Identifier Type: -

Identifier Source: org_study_id