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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02555293
Recruitment Status : Active, not recruiting
First Posted : September 21, 2015
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
RWTH Aachen University

Tracking Information
First Submitted Date  ICMJE September 14, 2015
First Posted Date  ICMJE September 21, 2015
Last Update Posted Date October 8, 2020
Study Start Date  ICMJE February 2016
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2015)
  • 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
  • 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
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Administration of Rifaximin to Improve Liver Regeneration and Outcome Following Major Liver Resection
Official Title  ICMJE Administration of Rifaximin to Improve Liver Regeneration and Outcome Following Major Liver Resection
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Liver Disease
  • Major Liver Resection
Intervention  ICMJE Drug: XIFAXAN® (Rifaximin)
Other Name: NDA 22-554
Study Arms  ICMJE
  • 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.
    Intervention: Drug: XIFAXAN® (Rifaximin)
  • No Intervention: standard therapy
    Patients directed to the control group will not receive Rifaximin.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 17, 2015)
96
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02555293
Other Study ID Numbers  ICMJE CTC-A 13-129
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party RWTH Aachen University
Study Sponsor  ICMJE RWTH Aachen University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account RWTH Aachen University
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP