HRS-AKI Treatment With TIPS in Patients With Cirrhosis

NCT05346393 | Recruiting DMC

• 3 other identifiers: ZKSJ0146DE-22-00013779431667134
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 14

Brief Summary

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).

Conditions

Cirrhosis, Liver; Hepatorenal Syndrome; Acute Kidney Injury; Ascites Hepatic

Keywords

Ascites; Acute Kidney Injury; Cirrhosis; Hepatorenal Syndrome; TIPS; transjugular intrahepatic portosystemic shunt; Terlipressin

Outcome Measures

Primary Outcomes (1)

• 12 month Liver transplant-free survival

  12 month Liver transplant-free survival

  12 months after Baseline

Secondary Outcomes (21)

• 3-month liver transplant free survival

  3 months after Baseline

• Number of patient which develop an indication for TIPS placement (variceal bleeding or refractory ascites) or TIPS revision (variceal bleeding or development of ascites) during follow-up

  within 12 months after Baseline

• Development of further decompensation of HRS-AKI during follow-up

  within 12 months after Baseline

• Reversal of HRS-AKI-AKI 3 MFU

  3 months after Baseline

• Reversal of HRS-AKI-AKI 12 MFU

  12 months after Baseline

Study Arms (2)

TIPS group

EXPERIMENTAL

TIPS implant (transjugular intrahepatic portosystemic shunt)

Procedure: TIPS

Control group

ACTIVE COMPARATOR

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

Drug: Standard of Care

Interventions

TIPS PROCEDURE

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

TIPS group

Standard of Care 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.

Also known as: Terlipressin + Albumin

Control group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with cirrhosis confirmed by histology or liver stiffness or with unequivocal signs in ultrasound, endoscopy and/or blood tests
• Clinically evident ascites due to portal hypertension
• HRS-AKI
• Age: ≥ 18 to ≤ 80 years old at the time of consent
• ECOG \< 4 prior to hospital admission
• 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.
• 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.

You may not qualify if:

• Recent or current use of nephrotoxic drugs (NSAIDS, Aminoglycosides or high-dosed iodinated contrast medium) in the previous 72 hours before AKI diagnosis
• Improvement of renal function after 1 day of diuretic removal and plasma volume expansion with albumin 1-1.5 gr/kg
• Uncontrolled shock within the last 48 hours prior to randomization
• 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.
• 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.)
• 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)
• Patients with cavernous portal vein thrombosis, splenic vein thrombosis or mesenteric vein thrombosis
• Patients with clinically significant cardiac disease (NYHA ≥ II)
• Patients with diastolic dysfunction grade 3.
• Patients with a reduced systolic function with an ejection fraction ≤ 50 %
• Patients with ACLF grade 3
• Patients with creatinine value \> 442 µmol/L (≙ 5 mg/dL)
• Patients with an acute variceal bleeding at the time of screening who have indication for pre-emptive TIPS and/or terlipressin.
• 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
• Patients with hepatocellular carcinoma outside of the Milan criteria

Sponsors & Collaborators

• Jena University Hospital: lead
• German Research Foundation: collaborator
• University Hospital Halle (Saale): collaborator

Study Sites (14)

University Hospital RWTH Aachen

Aachen, 52074, Germany

RECRUITING

Charité - Universitätsmedizin Berlin CVK

Berlin, 13353, Germany

NOT YET RECRUITING

University Hospital Dresden, Medical Clinic I, Gastroenterology

Dresden, 01307, Germany

RECRUITING

Universitätsklinikum Essen (AöR)

Essen, 45147, Germany

NOT YET RECRUITING

University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

RECRUITING

University Hospital Halle

Halle, 06120, Germany

RECRUITING

University Hospital Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

Medical University Hannover

Hanover, 30625, Germany

RECRUITING

Jena University Hospital, Clinic for Inner Medicine IV

Jena, 07747, Germany

RECRUITING

Klinikum Landshut AdöR der Stadt Landshut

Landshut, 84034, Germany

NOT YET RECRUITING

University Hospital Leipzig

Leipzig, 04103, Germany

NOT YET RECRUITING

RKH Clinic Ludwigsburg

Ludwigsburg, 71640, Germany

RECRUITING

Ludwig-Maximilians-University, Klinikum Großhadern

Munich, 81377, Germany

RECRUITING

University Hospital Münster, Medical Clinic B

Münster, 48149, Germany

RECRUITING

Related Publications (2)

• 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.

  PMID: 38235907 DERIVED

• 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.

  PMID: 37020315 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Hepatorenal Syndrome; Acute Kidney Injury; Ascites; Fibrosis

Interventions

Portasystemic Shunt, Transjugular Intrahepatic; Standard of Care; Terlipressin; Albumins

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Renal Insufficiency

Intervention Hierarchy (Ancestors)

Portasystemic Shunt, Surgical; Anastomosis, Surgical; Surgical Procedures, Operative; Vascular Grafting; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation; Lypressin; Vasopressins; Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Cristina Ripoll, Prof. Dr.

  Jena University Hospital

  STUDY DIRECTOR

Central Study Contacts

Cristina Ripoll, Prof. Dr.

CONTACT

+4936419; cristina.ripoll@med.uni-jena.de

Alexander Zipprich, Prof. Dr.

CONTACT

+4936419; alexander.zipprich@med.uni-jena.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: Parallel Assignment 1:1-randomization, parallel design, stratified by center and AKI stage.

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 26, 2022
• Study Start: November 29, 2022
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

DE (14)