HRS-AKI Treatment With TIPS in Patients With Cirrhosis

NCT ID: NCT05346393

Last Updated: 2024-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

124 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-11-29

Study Completion Date

2026-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

The study compares the effectiveness and safety of TIPS implantation in patients with HRS-AKI (stage1, 2 and 3) and liver cirrhosis with standard therapy (drug therapy with terlipressin + albumin).

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Cirrhosis is a major cause of global health burden worldwide. Acute kidney injury (AKI) occurs in 20% of hospitalized patients with cirrhosis. Acute kidney injury is a relatively new definition of renal failure which takes into account the dynamic changes in serum creatinine. Among the causes of AKI, hepatorenal syndrome-AKI has the worst prognosis. HRS-AKI is an acute condition which occurs in patients with ascites, mainly refractory ascites. HRS-AKI includes the traditional hepatorenal syndrome type 1, which was defined by a serum creatinine cutoff and which has an ominous prognosis when left untreated, nevertheless HRS-AKI also includes milder forms of renal failure.

The standard treatment of HRS-AKI is with the infusion of albumin and terlipressin. Although this treatment improves renal function, patients remain at risk for new episodes of HRS-AKI and liver transplantation should be considered. Nevertheless, this optimal solution is only a reality for a privileged few given the shortage of organs and the common presence of contraindications.

Development of HRS-AKI is caused by increased pressure in the portal vein (the vein which brings the blood from the intestines to the liver), among other factors. Increased pressure in the portal vein, also called portal hypertension, is one of the main pathophysiological mechanisms that lead to the different complications of cirrhosis. Transjugular intrahepatic portosystemic shunt (TIPS) is an interventional radiological procedure which reduces the pressure in the portal vein by creating a short-cut between the portal vein and the hepatic vein, the vein which brings the blood from the liver towards the heart. TIPS placement has become the mainstay of treatment of some complications of cirrhosis, namely variceal bleeding and refractory ascites. Although rationally plausible, the use of TIPS in HRS-AKI has not been evaluated in the context of randomized controlled trials. Indirect data suggest that it could be helpful, since patients who become TIPS have an improvement in renal hemodynamics and renal function as well as less episodes of HRS-AKI in the follow-up. On the other hand, traditional HRS type 1 can be associated to liver failure and cardiac alterations which contraindicate TIPS placement. HRS-AKI includes not only traditional HRS type 1, but also milder forms of the disease, so that it is reasonable to consider that TIPS placement may have a role in this condition.

This study is a multicenter (14 centers), prospective, randomized controlled trial which evaluates use of TIPS in patients with HRS-AKI (stage 1, 2 and 3) versus standard of care (albumin and terlipressin). Patients with cirrhosis and HRS-AKI who fulfill the inclusion criteria and do not have any exclusion criteria will be randomized to standard of care or standard of care and TIPS. Patients will be followed for a minimum of 12 months until the end of the trial. The main end-point is to compare the survival at the end of follow-up among the two groups.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cirrhosis, Liver Hepatorenal Syndrome Acute Kidney Injury Ascites Hepatic

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel Assignment 1:1-randomization, parallel design, stratified by center and AKI stage.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

TIPS group

TIPS implant (transjugular intrahepatic portosystemic shunt)

Group Type EXPERIMENTAL

TIPS

Intervention Type PROCEDURE

A transjugular intrahepatic portosystemic shunt (TIPS) is implanted into the cirrhotic liver

Control group

Standard medication therapy with terlipressin and albumin. In the case Terlipressin is not tolerated treatment with Noradrenaline may be considered following actual guidelines.

Group Type ACTIVE_COMPARATOR

Standard of Care

Intervention Type DRUG

Terlipressin/Albumin treatment is the preferred standard of care treatment. In the case Terlipressin is not tolerated treatment with Noradrenaline may be considered following actual guidelines.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TIPS

A transjugular intrahepatic portosystemic shunt (TIPS) is implanted into the cirrhotic liver

Intervention Type PROCEDURE

Standard of Care

Terlipressin/Albumin treatment is the preferred standard of care treatment. In the case Terlipressin is not tolerated treatment with Noradrenaline may be considered following actual guidelines.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Terlipressin + Albumin

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1. Patients with cirrhosis confirmed by histology or liver stiffness or with unequivocal signs in ultrasound, endoscopy and/or blood tests
2. Clinically evident ascites due to portal hypertension
3. HRS-AKI
4. Age: ≥ 18 to ≤ 80 years old at the time of consent
5. ECOG \< 4 prior to hospital admission
6. Subject has been informed of the nature of the study, is willing to comply with all required follow-up evaluations within the defined follow-up visit windows and has signed an Ethics Committee (EC) approved consent form.
7. Female subjects of childbearing potential have a negative pregnancy test ≤ 7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation. Female subjects will be exempted from this requirement in case they are sterile, infertile, or have been post-menopausal for at least 12 months (no menses). A contraceptive method with a pearl index below 1% is assumed to be effective.

Exclusion Criteria

1. Recent or current use of nephrotoxic drugs (NSAIDS, Aminoglycosides or high-dosed iodinated contrast medium) in the previous 72 hours before AKI diagnosis
2. Improvement of renal function after 1 day of diuretic removal and plasma volume expansion with albumin 1-1.5 gr/kg
3. Uncontrolled shock within the last 48 hours prior to randomization
4. Patients with uncontrolled infection (defined by a 20 % increase in inflam-matory parameters (CRP, leucocytes or insufficient decrease of PMN in ascitic fluid \< 25 % from baseline in the case of a SBP) despite 48 hours of antibiotic treatment.
5. Patients with cardiac cirrhosis as defined by the development of cirrhosis in a patient with chronic heart failure due to a primary cardiac disease (is-chemic cardiomyopathy, hypertensive cardiomyopathy, etc.)
6. Patients with contraindications to TIPS placement (e.g. Bilirubin \> 85.5 µmol/L (≙ 5 mg/dL), recurrent hepatic encephalopathy, clinically relevant pulmonary hypertension, aortic stenosis)
7. Patients with cavernous portal vein thrombosis, splenic vein thrombosis or mesenteric vein thrombosis
8. Patients with clinically significant cardiac disease (NYHA ≥ II)
9. Patients with diastolic dysfunction grade 3.
10. Patients with a reduced systolic function with an ejection fraction ≤ 50 %
11. Patients with ACLF grade 3
12. Patients with creatinine value \> 442 µmol/L (≙ 5 mg/dL)
13. Patients with an acute variceal bleeding at the time of screening who have indication for pre-emptive TIPS and/or terlipressin.
14. Patients with refractory ascites as defined by the International Ascites Club (\< 800 gr weight loss over 4 days in patients on low salt diet and high dose diuretics (spironolactone 400 mg /day and furosemide \* 160 mg /day), or lower dose of diuretics with complications secondary to the use of diuretics such as hyponatremia, renal failure, hepatic encephalopathy. \*equivalent dose of torasemide 40 mg/day
15. Patients with hepatocellular carcinoma outside of the Milan criteria
16. Patients with hepatocellular carcinoma within the Milan criteria in whom the tumor is located in the puncture tract.
17. Patients with benign liver tumors (except regenerative nodules) which are located in the puncture tract.
18. Patients who already have a TIPS placed
19. Patients who already had a liver transplantation
20. Patients with other comorbidities that lead to an estimated life expectancy under 1 year.
21. Patients with respiratory insufficiency which requires mechanical ventila-tion
22. Patients with circulatory failure which requires administration of other vas-opressors (catecholamines)
23. Patients receiving renal replacement therapy
24. The subject is currently enrolled in another investigational device or drug trial.
25. Patients with pregnancy or lactation
26. Patients which are suspected to be incompliant for study participation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

German Research Foundation

OTHER

Sponsor Role collaborator

University Hospital Halle (Saale)

UNKNOWN

Sponsor Role collaborator

Jena University Hospital

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Cristina Ripoll

Prof. Dr.

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Cristina Ripoll, Prof. Dr.

Role: STUDY_DIRECTOR

Jena University Hospital

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University Hospital RWTH Aachen

Aachen, , Germany

Site Status RECRUITING

Charité - Universitätsmedizin Berlin CVK

Berlin, , Germany

Site Status NOT_YET_RECRUITING

University Hospital Dresden, Medical Clinic I, Gastroenterology

Dresden, , Germany

Site Status RECRUITING

Universitätsklinikum Essen (AöR)

Essen, , Germany

Site Status NOT_YET_RECRUITING

University Hospital Freiburg

Freiburg im Breisgau, , Germany

Site Status RECRUITING

University Hospital Halle

Halle, , Germany

Site Status RECRUITING

University Hospital Hamburg-Eppendorf

Hamburg, , Germany

Site Status RECRUITING

Medical University Hannover

Hanover, , Germany

Site Status RECRUITING

Jena University Hospital, Clinic for Inner Medicine IV

Jena, , Germany

Site Status RECRUITING

Klinikum Landshut AdöR der Stadt Landshut

Landshut, , Germany

Site Status NOT_YET_RECRUITING

University Hospital Leipzig

Leipzig, , Germany

Site Status NOT_YET_RECRUITING

RKH Clinic Ludwigsburg

Ludwigsburg, , Germany

Site Status RECRUITING

Ludwig-Maximilians-University, Klinikum Großhadern

Munich, , Germany

Site Status RECRUITING

University Hospital Münster, Medical Clinic B

Münster, , Germany

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Germany

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Cristina Ripoll, Prof. Dr.

Role: CONTACT

+4936419 ext. 32 44 01

Alexander Zipprich, Prof. Dr.

Role: CONTACT

+4936419 ext. 32 44 01

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Tony Bruns, Prof. Dr.

Role: primary

Cornelius Engelmann, PD Dr.

Role: primary

Marco Berning, Dr.

Role: primary

+49 351 458 ext. 5643

Jassin Rashidi Alavijeh, PD Dr.

Role: primary

Dominik Bettinger, PD Dr.

Role: primary

Marko Damm, Dr.

Role: primary

Andreas Drolz, PD Dr.

Role: primary

+49 40 7410 ext. 53910

Benjamin Maasoumy, PD Dr.

Role: primary

+49 511532 ext. 6814

Cristina Ripoll, Prof. Dr.

Role: primary

+4936419 ext. 324401

Matthias Dollinger, Prof. Dr.

Role: primary

Thomas Berg, Prof. Dr.

Role: primary

+49 0341 97 ext. 24831

Karel Caca, Prof. Dr.

Role: primary

+49 7141 99 ext. 67201

Christian Lange, Prof. Dr.

Role: primary

Jonel Trebicka, Prof. Dr.

Role: primary

+49 251 83 ext. 57562

References

Explore related publications, articles, or registry entries linked to this study.

Gonzalez-Garay AG, Serralde-Zuniga AE, Velasco Hidalgo L, Flores Garcia NC, Aguirre-Salgado MI. Transjugular intrahepatic portosystemic shunts for adults with hepatorenal syndrome. Cochrane Database Syst Rev. 2024 Jan 18;1(1):CD011039. doi: 10.1002/14651858.CD011039.pub2.

Reference Type DERIVED
PMID: 38235907 (View on PubMed)

Ripoll C, Platzer S, Franken P, Aschenbach R, Wienke A, Schuhmacher U, Teichgraber U, Stallmach A, Steighardt J, Zipprich A; Liver-HERO Study Group. Liver-HERO: hepatorenal syndrome-acute kidney injury (HRS-AKI) treatment with transjugular intrahepatic portosystemic shunt in patients with cirrhosis-a randomized controlled trial. Trials. 2023 Apr 5;24(1):258. doi: 10.1186/s13063-023-07261-9.

Reference Type DERIVED
PMID: 37020315 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

DE-22-00013779

Identifier Type: OTHER

Identifier Source: secondary_id

431667134

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

ZKSJ0146

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Freiburg TIPS Registry
NCT05782556 RECRUITING
Outcome After TIPS
NCT03459378 COMPLETED
Early TIPS for Ascites Study
NCT01236339 TERMINATED NA
AI-guided TIPS Procedure
NCT06837974 NOT_YET_RECRUITING NA