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Cirrhosis, LiverLiver-HERONCT05346393

HRS-AKI Treatment With TIPS in Patients With Cirrhosis

A study testing TIPS in people with Cirrhosis, Liver and Hepatorenal Syndrome, run by Jena University Hospital at 14 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 80 years
What is being tested?
TIPS
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
124 participants
Where
14 sitesGermany
Study dates
29 Nov 2022to Jun 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

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 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.

Who cannot join

  • 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)
Show all 26Show fewer
  • 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
  • Patients with hepatocellular carcinoma within the Milan criteria in whom the tumor is located in the puncture tract.
  • Patients with benign liver tumors (except regenerative nodules) which are located in the puncture tract.
  • Patients who already have a TIPS placed
  • Patients who already had a liver transplantation
  • Patients with other comorbidities that lead to an estimated life expectancy under 1 year.
  • Patients with respiratory insufficiency which requires mechanical ventila-tion
  • Patients with circulatory failure which requires administration of other vas-opressors (catecholamines)
  • Patients receiving renal replacement therapy
  • The subject is currently enrolled in another investigational device or drug trial.
  • Patients with pregnancy or lactation
  • Patients which are suspected to be incompliant for study participation.

Trial locations and contacts

14 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Cristina Ripoll, Prof. Dr. contact

+4936419 ext. 32 44 01

cristina.ripoll@med.uni-jena.de

Alexander Zipprich, Prof. Dr. contact

+4936419 ext. 32 44 01

alexander.zipprich@med.uni-jena.de

14 sites in 1 country

Germany14 sites, 14 recruiting

  • University Hospital RWTH Aachen

    Aachen, 52074

    Tony Bruns, Prof. Dr., tbruns@ukaachen.de

    Recruiting

  • Charité - Universitätsmedizin Berlin CVK

    Berlin, 13353

    Cornelius Engelmann, PD Dr.

    Not yet recruiting

  • University Hospital Dresden, Medical Clinic I, Gastroenterology

    Dresden, 01307

    Marco Berning, Dr., +49 351 458 ext. 5643, Marco.Berning@uniklinikum-dresden.de

    Recruiting

  • Universitätsklinikum Essen (AöR)

    Essen, 45147

    Jassin Rashidi Alavijeh, PD Dr.

    Not yet recruiting

  • University Hospital Freiburg

    Freiburg im Breisgau, 79106

    Dominik Bettinger, PD Dr., dominik.bettinger@uniklinik-freiburg.de

    Recruiting

  • University Hospital Halle

    Halle, 06120

    Marko Damm, Dr.

    Recruiting

  • University Hospital Hamburg-Eppendorf

    Hamburg, 20246

    Andreas Drolz, PD Dr., +49 40 7410 ext. 53910, a.drolz@uke.de

    Recruiting

  • Medical University Hannover

    Hanover, 30625

    Benjamin Maasoumy, PD Dr., +49 511532 ext. 6814, Maasoumy.Benjamin@mh-hannover.de

    Recruiting

  • Jena University Hospital, Clinic for Inner Medicine IV

    Jena, 07747

    Cristina Ripoll, Prof. Dr., +4936419 ext. 324401, cristina.ripoll@med.uni-jena.de

    Recruiting

  • Klinikum Landshut AdöR der Stadt Landshut

    Landshut, 84034

    Matthias Dollinger, Prof. Dr.

    Not yet recruiting

  • University Hospital Leipzig

    Leipzig, 04103

    Thomas Berg, Prof. Dr., +49 0341 97 ext. 24831, studien-hepatologie@medizin.uni-leipzig.de

    Not yet recruiting

  • RKH Clinic Ludwigsburg

    Ludwigsburg, 71640

    Karel Caca, Prof. Dr., +49 7141 99 ext. 67201, karel.caca@rkh-kliniken.de

    Recruiting

  • Ludwig-Maximilians-University, Klinikum Großhadern

    Munich, 81377

    Christian Lange, Prof. Dr., Christian.Lange@med.uni-muenchen.de

    Recruiting

  • University Hospital Münster, Medical Clinic B

    Münster, 48149

    Jonel Trebicka, Prof. Dr., +49 251 83 ext. 57562, jonel.trebicka@ukmuenster.de

    Recruiting

Other trials in Germany

About this study

Official title: Hepatorenal Syndrome-acute Kidney Injury (HRS-AKI) Treatment With Transjugular Intrahepatic Portosystemic Shunt in Patients With Cirrhosis. A Randomized Controlled Trial

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).

Read the detailed description

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.

Being tested
TIPS, Standard of Care
Keywords
Ascites, Acute Kidney Injury, Cirrhosis, Hepatorenal Syndrome, TIPS, transjugular intrahepatic portosystemic shunt, Terlipressin
Medical subject headings
Liver Cirrhosis, Hepatorenal Syndrome, Acute Kidney Injury, Ascites, Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TIPSProcedure or surgery

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

  • Standard of CareDrug

    Also called Terlipressin + Albumin

    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.

Study groups in NCT05346393
Study groupRoleWhat they receive
TIPS groupExperimentalTIPS implant (transjugular intrahepatic portosystemic shunt)
Receives: Procedure: TIPS
Control groupActive comparatorStandard medication therapy with terlipressin and albumin. In the case Terlipressin is not tolerated treatment with Noradrenaline may be considered following actual guidelines.
Receives: Drug: Standard of Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 12 month Liver transplant-free survival

    12 month Liver transplant-free survival

    Measured: 12 months after Baseline

Secondary outcomes (21)

  1. 3-month liver transplant free survival

    3-month liver transplant free survival

    Measured: 3 months after Baseline

  2. 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

    Number of patient which develop an indication for TIPS placement according to clinical guidelines (such as variceal bleeding or refractory ascites) in the control group or indication for a TIPS revision (variceal bleeding, development of ascites) in the intervention group will be assessed during the 12 months follow-up

    Measured: within 12 months after Baseline

  3. Development of further decompensation of HRS-AKI during follow-up

    Development of further decompensation as defined in the Baveno VII Consensus Workshop (e.g. overt hepatic encephalopathy, refractory or recurrent ascites, dilutional hyponatremia, new AKI-HRS, variceal bleeding) during follow-up

    Measured: within 12 months after Baseline

  4. Reversal of HRS-AKI-AKI 3 MFU

    Reversal of HRS-AKI-AKI at 3 months (vs. baseline), defined as return of serum creatinine level within 0.3 mg/dl (26 mmol/L).

    Measured: 3 months after Baseline

  5. Reversal of HRS-AKI-AKI 12 MFU

    Reversal of HRS-AKI-AKI at 12 months (vs. baseline), defined as return of serum creatinine level within 0.3 mg/dl (26 mmol/L).

    Measured: 12 months after Baseline

  6. Partial response to treatment 3 MFU

    Partial response to treatment at 3 months (vs. baseline) defined as reduction of at least one AKI stage with decrease of serum creatinine to ≥ 0.3 mg/dl (26 mmol/L) above the baseline value.

    Measured: 3 months after Baseline

  7. Partial response to treatment 12 MFU

    Partial response to treatment at 12 months (vs. baseline) defined as reduction of at least one AKI stage with decrease of serum creatinine to ≥ 0.3 mg/dl (26 mmol/L) above the baseline value.

    Measured: 12 months after Baseline

  8. In-hospital survival

    In-hospital survival of the patients (patients are hospitalized for diagnosis of HRS-AKI and start of treatment - due to poor diagnosis, patients may die during hospital stay)

    Measured: baseline until 12 months

  9. 28-day survival

    28-day survival

    Measured: baseline until day 28 after baseline

  10. 90-day survival

    90-day survival

    Measured: baseline until day 90 after baseline

  11. Length of in-hospital-stay

    Length of in-hospital-stay of the patients (patients are hospitalized for diagnosis of HRS-AKI and start of treatment)

    Measured: baseline until 12 months

  12. Changes in HrQoL as measured by SF36 3 MFU

    Relative changes in Health-related Quality of Life as measured by SF36 at 3 months (vs. baseline)

    Measured: 3 months after Baseline

  13. Changes in HrQoL as measured by SF36 12 MFU

    Relative changes in Health-related Quality of Life as measured by SF36 at 12 months (vs. baseline)

    Measured: 12 months after Baseline

  14. Changes in HrQoL as measured by CLDQ 3 MFU

    Relative changes in Health-related Quality of Life as measured by CLDQ (Chronic Liver Disease Questionnaire) at 3 months (vs. baseline)

    Measured: 3 months after Baseline

  15. Changes in HrQoL as measured by CLDQ 12 MFU

    Relative changes in Health-related Quality of Life as measured by CLDQ (Chronic Liver Disease Questionnaire) at 12 months (vs. baseline)

    Measured: 12 months after Baseline

  16. Need for renal replacement therapy

    Need for renal replacement therapy within Follow-up

    Measured: 12 months after Baseline

  17. recurrence of HRS-AKI after treatment at 3 months

    recurrence of HRS-AKI after treatment at 3 months

    Measured: 3 months after Baseline

  18. recurrence of HRS-AKI after treatment at 12 months

    recurrence of HRS-AKI after treatment at 12 months

    Measured: 12 months after Baseline

  19. Safety Assessment

    Number of AEs and SAEs in each group with special attention on the development of acute on chronic liver failure and signs of heart failure.

    Measured: 12 months after Baseline

  20. Development of acute-on-chronic liver failure during follow-up

    Development of acute-on-chronic liver failure during follow-up

    Measured: 12 months after Baseline

  21. Impact of the presence of intrinsic nephropathy as assessed by cystatin C and UnGAL on outcomes (survival and reversal of AKI)

    Patients with clear intrinsic nephropathy will be excluded from the study, as the diagnosis of hepatorenal syndrome requires exclusion of intrinsic nephropathy. Nevertheless, patients with HRS may also have other conditions that may lead to a subclinical chronic nephropathy. This will be assessed with cystitis C and/or UnGAL and its association with survival and reversal of AKI. This is a secondary exploratory end-point

    Measured: 12 months after Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Apr 2022
  2. Study start29 Nov 2022
  3. Primary completionJun 2025 (estimated)
  4. Study completionJun 2026 (estimated)

Resources

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 N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Parallel Assignment 1:1-randomization, parallel design, stratified by center and AKI stage.
Masking
None (open label)
Enrolment
124 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05346393
Sponsor's protocol ID
ZKSJ0146
Other IDs
DE-22-00013779, 431667134
Acronym
Liver-HERO
Status last verified
Nov 2024
First submitted
1 Apr 2022
Last updated
18 Nov 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 38235907

  • 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.

    PubMed 37020315

Questions about this trial

What is this clinical trial studying?

A study testing TIPS in people with Cirrhosis, Liver and Hepatorenal Syndrome, run by Jena University Hospital at 14 sites 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 7 inclusion and 26 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: looking for participants now, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites 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.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Cristina Ripoll, Prof. Dr. (+4936419 ext. 32 44 01, cristina.ripoll@med.uni-jena.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

12 month Liver transplant-free survival (time frame: 12 months after Baseline). 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 NCT05346393, which also lists 2 linked publications.

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 18 Nov 2024.

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