Clinical trial NCT02555293: Administration of Rifaximin to Improve Liver Regeneration and Outcome Following Major Liver Resection
Official title: Administration of Rifaximin to Improve Liver Regeneration and Outcome Following Major Liver Resection
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Malignant Liver Disease
Major Liver Resection
Keywords: Liver resection
fibrosis
inflammation
Rifaximin
Lead sponsor: RWTH Aachen University
Sponsor class: OTHER
First posted: 2015-09-21
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Effect of Rifaximin on postoperative liver function
timeFrame: Postoperative day 7 in relation to postoperative day 4
Secondary outcomes:
measure: postoperative morbidity/Complications
timeFrame: minimum 14 days after liver resection
measure: Liver volume percentage increase
timeFrame: 14 up to 21 days before liver resection at baseline and 7 days after the operation
measure: liver function percentage increase
timeFrame: 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)
measure: Time to functional recovery
timeFrame: minimum 14 days starting on operation day
Other outcomes:
Locations:
city: Aachen
country: Germany
facility: RWTH Aachen University
Study officials:
References:
citation: 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.