MRI to Assess the Effect of Non-selective Beta-blocker in Patients With Cirrhosis

March 13, 2023 updated by: Flemming Bendtsen, Hvidovre University Hospital

Hemodynamic Alterations in Liver Cirrhosis Validated by Non-invasive MRI Compared to Invasive Assessment: Can MRI and Echocardiography Predict the Pharmacological Response of Non-selective Beta-blocker in Patients With Cirrhosis?

Background:

Standardization and new therapeutic treatments of variceal bleeding has significantly reduced the mortality the last 25 years, but there is still a high 6-week mortality around 15-20% and 1-year mortality of about 40%. Cirrhotic patients without prophylactic treatment suffer a risk of 60% of re-bleeding within the first year after the first bleeding episode. Variceal ligation and NSBB are the standard therapy as secondary prophylaxis, while only non-selective beta-blocker (NSBB) is offered as first-line therapy in primary prophylaxis. If portal pressure is reduced to a value below 12 mmHg or by 20% (10% if assessed by intravenous administrations), the risk of bleeding is substantially reduced, but not all patients respond to the treatment with propranolol (40-50%). Hence, patients who are non-responders to NSBB should be offered alternative treatment with e.g. carvedilol, which is a combined alpha-beta-receptor blocker or endoscopic band ligation. Currently, the response to NSBB is assessed invasively during a liver vein catheterization (LVC). Unfortunately, only a few centres in the world can perform this procedure and there are no reliable non-invasive alternatives to assess the respond to NSBB, which is of extreme importance, since non-responders have three fold increased risk of a new variceal bleeding episode.

Aim:

In general the aim of the project is to develop faster and non-invasive methods to evaluate portal hypertension and individual pharmacological response of NSBB in patients with cirrhosis. Furthermore, we expect to detect changes in liver and spleen stiffness as measured by MR-Elastography (MRE) after NSBB and that these depend on the drug-related effects on portal pressure.

Study design and patients:

39 patients with cirrhosis and esophageal varices that require NSBB (propranolol) treatment.

Patients are assessed with LVC, MR-scans, echocardiography and biochemical tests. LVC is the gold standard method to test if patients respond to propranolol treatment. At visit 1. the response to NSBB is defined as a reduction of HVPG ≥10%, or to a HVPG< 12mmHg after intravenous NSBB administrations during LVC. MRI-scan with intraveneus NSBB administration is performed at visit 2. Minimum 5 days of NSBB wash out between visit 1 and 2.

Study Overview

Status

Completed

Conditions

Detailed Description

MR-elastography and Phase Contrast MRI compared to LVC

Study Type

Observational

Enrollment (Actual)

40

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

39 patients with cirrhosis and esophageal varices that require NSBB (propranolol) treatment.

Description

Inclusion Criteria:

  • Patients with cirrhosis and esophageal varices that require NSBB treatment
  • Patients of more than 18 and less than 78 years of age
  • Patients with a portal pressure HVPG ≥ 12mmHg

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
NSBB response defined as a reduction in HVPG >10% or HVPG <12 mmHG after intraveneus NSBB administrations compared to flow (mL/min) in splanchnic vessels
Time Frame: after 20 minutes respons time
To assess if changes in MR flow induced with NSBB (propranolol) administrations can predict the changes in HVPG after NSBB administration (NSBB respons) assessed by LVC
after 20 minutes respons time

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
MR-elastography
Time Frame: after 20 minutes
To assess the liver and spleen stiffness (kPa) with MRE before and after intraveneus NSBB administration
after 20 minutes

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hvidovre University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2017

Primary Completion (Actual)

December 8, 2020

Study Completion (Actual)

December 8, 2020

Study Registration Dates

First Submitted

February 10, 2018

First Submitted That Met QC Criteria

February 18, 2018

First Posted (Actual)

February 20, 2018

Study Record Updates

Last Update Posted (Actual)

March 14, 2023

Last Update Submitted That Met QC Criteria

March 13, 2023

Last Verified

March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 16048475

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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