Malignant Liver DiseasePhase 2ARROWNCT02555293
Administration of Rifaximin to Improve Liver Regeneration and Outcome Following Major Liver Resection
A Phase 2 study testing XIFAXAN® (Rifaximin) in people with Malignant Liver Disease and Major Liver Resection, run by RWTH Aachen University at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Malignant Liver Disease, Major Liver Resection
- What is being tested?
- XIFAXAN® (Rifaximin)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2016to 20 Nov 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing a liver resection of at least 4 segments
- Age > 18 years < 80 years
- BMI 18-40
- Patients with ASA (American Society of Anesthesiologists) I-III
- Written informed consent prior to study participation
Who cannot join
- Patients with ASA IV-V
- Contraindication for MRI (see 5.4.3)
- Underlying chronic liver disease such as severe fibrosis or liver cirrhosis
- Need for procedures additive to partial liver resection
- Participation in other liver related trials
- BMI > 40
Show all 19Show fewer
- Previous liver transplantation or porto-systemic shunt
- Concomitant acute infectious diseases
- Renal insufficiency
- Hypersensitivity to Rifaximin
- Concomitant HIPEC (hypertherme intraperitoneale chemoperfusion) treatment
- ALPPS (associating liver partition and portal vein ligation for staged hepatectomy)
- 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.
- Lactating females
- 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.
- The subject received an investigational drug within 30 days prior to inclusion into this study
- 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
- The subject is unwilling or unable to follow the procedures outlined in the protocol
- The subject is mentally or legally incapacitated
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- XIFAXAN® (Rifaximin)
- Keywords
- Liver resection, fibrosis, inflammation, Rifaximin
- Medical subject headings
- Fibrosis, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XIFAXAN® (Rifaximin)Drug
Also called NDA 22-554
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: XIFAXAN® (Rifaximin) |
| standard therapy | No intervention | Patients directed to the control group will not receive Rifaximin. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Postoperative day 7 in relation to postoperative day 4
Secondary outcomes (4)
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
Measured: minimum 14 days after liver resection
Liver volume percentage increase
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
Measured: 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.
Measured: 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
- 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.
Measured: minimum 14 days starting on operation day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2015 (estimated)
- Study startFeb 2016
- Primary completion20 Nov 2020
- Study completion20 Nov 2020
Why it stopped: Prematurely terminated due to organisational reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Malignant Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RWTH Aachen University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02555293
- Sponsor's protocol ID
- CTC-A 13-129
- Acronym
- ARROW
- Status last verified
- Oct 2020
- First submitted
- 14 Sep 2015
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
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.
PubMed 34504196
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Administration of Rifaximin to Improve Liver Regeneration and Outcome Following Major Liver Resection
- ClinicalTrials.gov ID
- NCT02555293
- Acronym / sponsor ID
- ARROW / CTC-A 13-129
- Conditions
- Malignant Liver Disease, Major Liver Resection
- Keywords
- Liver resection, fibrosis, inflammation, Rifaximin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Prematurely terminated due to organisational reasons
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- RWTH Aachen UniversityUniversity, hospital or other
- Study start
- Feb 2016
- Primary completion
- 20 Nov 2020 (actual)
- Study completion
- 20 Nov 2020 (actual)
- First posted
- 21 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| film-coated Rifaximin (550 mg) | Experimental | Drug: XIFAXAN® (Rifaximin)(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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients undergoing a liver resection of at least 4 segments
- Age > 18 years < 80 years
- BMI 18-40
- Patients with ASA (American Society of Anesthesiologists) I-III
- Written informed consent prior to study participation
Key exclusion criteria (19 listed)
- Patients with ASA IV-V
- Contraindication for MRI (see 5.4.3)
- Underlying chronic liver disease such as severe fibrosis or liver cirrhosis
- Need for procedures additive to partial liver resection
- Participation in other liver related trials
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XIFAXAN® (Rifaximin)Also: NDA 22-554 | Drug | film-coated Rifaximin (550 mg) |
Primary outcome
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
4 secondary outcomes
postoperative morbidity/Complications
Time frame: 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
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)
Time to functional recovery
Time frame: minimum 14 days starting on operation day
Results and safety
The study was stopped early (reason given: Prematurely terminated due to organisational reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2021.
- Derived from this study: PubMed 34504196Bednarsch 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing XIFAXAN® (Rifaximin) in people with Malignant Liver Disease and Major Liver Resection, run by RWTH Aachen University at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Prematurely terminated due to organisational reasons). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of Rifaximin on postoperative liver function (time frame: Postoperative day 7 in relation to postoperative day 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02555293, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2021.