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Prematurely terminated due to organisational reasons
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| standard therapy | No Intervention | Patients directed to the control group will not receive Rifaximin. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| XIFAXAN® (Rifaximin) | Drug |
|
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| postoperative morbidity/Complications | Complications will be scored using the Clavien-Dindo scoring system and a liver-specific-composite-endpoint for the duration of hospital stay, an expected average of minimum 14 days | minimum 14 days after liver resection |
| Liver volume percentage increase |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| RWTH Aachen University | Aachen | 52074 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34504196 | Derived | 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. |
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| ID | Term |
|---|---|
| D005355 | Fibrosis |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D000078262 | Rifaximin |
| ID | Term |
|---|---|
| D012294 | Rifamycins |
| D006576 | Heterocyclic Compounds, 4 or More Rings |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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MRI volumetry: pre- and postoperative comperative measurements mainly based on suitable, preoperatively and routinely done MRI/CT-images. On postoperative day 7 as tudy related MRI will be done if no CT/MRI images available routinely done 1 day before or one day after visit 5 |
| 14 up to 21 days before liver resection at baseline and 7 days after the operation |
| liver function percentage increase | LiMAx-test: LiMAx liver function testing will be performed before surgery and on postoperative days 4 and 7 to evaluate functional recovery after liver resection. | 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 | The evaluation of time to functional recovery will start on POD 0 and will be scored daily until discharge from the hospital with the following criteria
| minimum 14 days starting on operation day |
| D047029 | Lactams, Macrocyclic |
| D047028 | Macrocyclic Compounds |
| D011083 | Polycyclic Compounds |