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

October 28, 2021 updated by: RWTH Aachen University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
96

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Aachen, Germany, 52074
        • RWTH Aachen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Drug: XIFAXAN® (Rifaximin)
Other Names:
  • NDA 22-554
No Intervention: standard therapy
Patients directed to the control group will not receive Rifaximin.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Effect of Rifaximin on postoperative liver function
Time Frame: Postoperative day 7 in relation to postoperative day 4

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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
postoperative morbidity/Complications
Time Frame: minimum 14 days after liver resection
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
Time Frame: 14 up to 21 days before liver resection at baseline and 7 days after the operation

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
Time Frame: 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)

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
Time Frame: minimum 14 days starting on operation day

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

  • Adequate pain control on oral analgesics only
  • Eating and drinking properly without the need of IV fluids
  • Independently mobile or mobile at preoperative level
  • Standard laboratory tests and liver function returning to normal level When all of these criteria are met, we consider a patient functional recovered.
minimum 14 days starting on operation day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
RWTH Aachen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 20, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 20, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 14, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 17, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 21, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 1, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 28, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CTC-A 13-129

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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