Current partner codePEPTIDESDE
NCT05346393·Not applicable·INTERVENTIONAL

HRS-AKI Treatment With TIPS in Patients With Cirrhosis

Status

Recruiting

Phase

Not applicable

Enrollment

124

Locations

14

Results

Not posted

Publications

2

Study summary

What the protocol is testing.

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).

Full 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.

Interventions

Treatment arms and agents.

PROCEDURE

TIPS

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

DRUG

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.

Timeline

From registration to results.

  1. First posted

    Apr 26, 2022

  2. Study start

    Nov 29, 2022

  3. Primary completion

    Jun 2025

  4. Study completion

    Jun 2026

  5. Results posted

    Not reported

  6. Registry updated

    Nov 18, 2024

Outcomes

What the study measures.

Primary outcomes

12 month Liver transplant-free survival

Time frame · 12 months after Baseline

12 month Liver transplant-free survival

Secondary outcomes

3-month liver transplant free survival

Time frame · 3 months after Baseline

3-month liver transplant free survival

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

Time frame · within 12 months after Baseline

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

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

Time frame · within 12 months after Baseline

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

Reversal of HRS-AKI-AKI 3 MFU

Time frame · 3 months after Baseline

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).

Reversal of HRS-AKI-AKI 12 MFU

Time frame · 12 months after Baseline

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).

Partial response to treatment 3 MFU

Time frame · 3 months after Baseline

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.

Partial response to treatment 12 MFU

Time frame · 12 months after Baseline

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.

In-hospital survival

Time frame · baseline until 12 months

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)

28-day survival

Time frame · baseline until day 28 after baseline

28-day survival

90-day survival

Time frame · baseline until day 90 after baseline

90-day survival

Eligibility

Who can take part.

Minimum age
18 Years
Maximum age
80 Years
Sex
ALL
Healthy volunteers
No

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.

Study locations

14 registered sites.

Germany. Showing up to 24 locations stored in the fast local snapshot.

University Hospital RWTH Aachen

Aachen, Germany

Charité - Universitätsmedizin Berlin CVK

Berlin, Germany

University Hospital Dresden, Medical Clinic I, Gastroenterology

Dresden, Germany

Universitätsklinikum Essen (AöR)

Essen, Germany

University Hospital Freiburg

Freiburg im Breisgau, Germany

University Hospital Halle

Halle, Germany

University Hospital Hamburg-Eppendorf

Hamburg, Germany

Medical University Hannover

Hanover, Germany

Jena University Hospital, Clinic for Inner Medicine IV

Jena, Germany

Klinikum Landshut AdöR der Stadt Landshut

Landshut, Germany

University Hospital Leipzig

Leipzig, Germany

RKH Clinic Ludwigsburg

Ludwigsburg, Germany

Ludwig-Maximilians-University, Klinikum Großhadern

Munich, Germany

University Hospital Münster, Medical Clinic B

Münster, Germany

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