MRI to Assess the Effect of Terlipressin in Patients With Acute Hepatorenal Syndrome (HRS-AKI)

MR-flow to Validate Hemodynamic Effect of Terlipressin in Patients With Acute Hepatorenal Syndrome: Can MRI and Echocardiography Predict the Pharmacological Response and Longterm Effect of Terlipressin?

Heptorenal syndrome (HRS) is divided into two types. A non-acute kidney injury (NAKI-HRS), which is predominantly related to end-stage disease and a more acute kidney injury (HRS-AKI). HRS-AKI is potentially reversible and develops subsequent to aggravation of a systemic circulatory vasodilatation, that triggers renal vasoconstriction and deteriorates renal perfusion and function. The albumin and terlipressin response is evaluated clinically, routinely for a week and reduces mortality with 23% compared to no treatment. Only 40-50% of the patients with HRS-AKI respond to the treatment with terlipressin.

The treatment of hepatorenal syndrome (HRS-AKI) is aimed at improving blood flow to the kidneys. Flow changes associated to development of HRS have only sparsely been studied and not previously by MR technique and no previous studies have evaluated changes in flow induced by terlipressin. It has been hypothesized that development of HRS is associated to a deterioration in heart function with development of cardiomyopathy, which together with renal vasoconstriction leads to renal failure. Simultaneous MR-assessments of cardiac function and flows (especially the renal flow) in HRS-AKI have not previously been performed.

The aim of the project is to develop new, fast and non-invasive methods to evaluate hemodynamic changes and individual pharmacological terlipressin response in patients with acute hepatorenal syndrome (type HRS-AKI)

We expect a higher increase in renal blood flow in terlipressin-responders compared to terlipressin-non-responders and non-responders will generally have a lower basic renal flow and a decreased cardiac output.

Study design and patients The study design is experimental and includes 30 cirrhotic patients with HRS-AKI. Patients with HRS-AKI are MR scanned before and 17 minutes after their first dose of terlipressin. ECHO is performed before first dose of Terlipressin and is repeated after one of the first doses of terlipressin. Clinically efficacy is defined in accordance to international guidelines at day-7 and 90 days mortality is registered. The screening period and treatments follow international and national guidelines for acute renal failure in patients with cirrhosis.

Study Overview

• Status: Completed
• Conditions: Liver Diseases; Cirrhosis; Acute Kidney Injury; Portal Hypertension; Liver Cirrhoses; Hepato-Renal Syndrome; Cirrhosis Cardiac

• Study Type: Observational
• Enrollment (Actual): 11

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Centre of Gastroenterology, Dept. of medicine. Hvidovre University Hospital
  • Capital Region
    • Hvidovre, Capital Region, Denmark, 2650
      • Hvidovre University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

30 patients with cirrhosis and acute kidney injury who meet the criteria for HRS-AKI and needs terlipressin treatment.

Description

Inclusion Criteria:

• Patients with cirrhosis and acute hepatorenal syndrome (HRS-AKI)
• Patient of more than 18 and less than 78 years of age

Exclusion Criteria:

• Patients who are unable to give informed consent
• Patients with absolute contraindication for MRI
• Patients with absolute contraindication for terlipressin
• Pregnant women
• Patient with severe hemodynamic comorbidity

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow (mL/min) in kidney and splanchnic vessels in patients with HRS-AKI and cirrhotic patients without kidney impairment	i) To characterize and compare changes in flow with MR and ECHO in patients with HRS-AKI compared to cirrhotic patients without kidney impairment	Baseline (mL/min)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow changes (mL/min) in HRS-AKI patients with terlipressin non-response vs. response.	To investigate whether flow changes measured with MR and echocardiography induced by a single dose of terlipressin can predict the clinical (7 days) response to terlipressin treatment. Full terlipressin response is if creatinine level returns to baseline after 7 days treatment. Partial response is a reduction in creatinine of 25% after 7 days terlipressin treatment	Response after 7 days treatment (mL/min)
Flow changes (mL/min) after terlipressin administration compared to mortality.	To investigate whether flow changes measured with MR and echocardiography induced by a single dose of terlipressin can predict the mortality after 90 days	90 days

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Investigators: Study Chair: Flemming Bendtsen, Hvidovre University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 8, 2018
• Primary Completion (ACTUAL): April 15, 2021
• Study Completion (ACTUAL): April 21, 2021

Study Registration Dates

• First Submitted: March 14, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (ACTUAL): March 30, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 16, 2021
• Last Update Submitted That Met QC Criteria: August 9, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Echocardiography; Terlipressin; Pharmacological respons; Hemodynamic assessments; Hepatorenal syndrome - acute kidney injury
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Kidney Diseases; Urologic Diseases; Disease; Renal Insufficiency; Liver Diseases; Fibrosis; Syndrome; Liver Cirrhosis; Acute Kidney Injury; Hypertension, Portal; Hepatorenal Syndrome
• Other Study ID Numbers: 17001401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No