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).
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
124
A transjugular intrahepatic portosystemic shunt (TIPS) is implanted into the cirrhotic liver
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.
University Hospital RWTH Aachen
Aachen, Germany
RECRUITINGCharité - Universitätsmedizin Berlin CVK
Berlin, Germany
12 month Liver transplant-free survival
12 month Liver transplant-free survival
Time frame: 12 months after Baseline
3-month liver transplant free survival
3-month liver transplant free survival
Time frame: 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
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
Time frame: within 12 months after Baseline
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
Time frame: within 12 months after Baseline
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).
Time frame: 3 months after Baseline
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).
Time frame: 12 months after Baseline
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University Hospital Dresden, Medical Clinic I, Gastroenterology
Dresden, Germany
RECRUITINGUniversitätsklinikum Essen (AöR)
Essen, Germany
NOT_YET_RECRUITINGUniversity Hospital Freiburg
Freiburg im Breisgau, Germany
RECRUITINGUniversity Hospital Halle
Halle, Germany
RECRUITINGUniversity Hospital Hamburg-Eppendorf
Hamburg, Germany
RECRUITINGMedical University Hannover
Hanover, Germany
RECRUITINGJena University Hospital, Clinic for Inner Medicine IV
Jena, Germany
RECRUITINGKlinikum Landshut AdöR der Stadt Landshut
Landshut, Germany
NOT_YET_RECRUITING...and 4 more locations
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.
Time frame: 3 months after Baseline
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.
Time frame: 12 months after Baseline
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)
Time frame: baseline until 12 months
28-day survival
28-day survival
Time frame: baseline until day 28 after baseline
90-day survival
90-day survival
Time frame: baseline until day 90 after baseline
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)
Time frame: baseline until 12 months
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)
Time frame: 3 months after Baseline
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)
Time frame: 12 months after Baseline
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)
Time frame: 3 months after Baseline
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)
Time frame: 12 months after Baseline
Need for renal replacement therapy
Need for renal replacement therapy within Follow-up
Time frame: 12 months after Baseline
recurrence of HRS-AKI after treatment at 3 months
recurrence of HRS-AKI after treatment at 3 months
Time frame: 3 months after Baseline
recurrence of HRS-AKI after treatment at 12 months
recurrence of HRS-AKI after treatment at 12 months
Time frame: 12 months after Baseline
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.
Time frame: 12 months after Baseline
Development of acute-on-chronic liver failure during follow-up
Development of acute-on-chronic liver failure during follow-up
Time frame: 12 months after Baseline
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
Time frame: 12 months after Baseline