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

Completed

• Conditions: Portal Hypertension; Cirrhosis; Liver Cirrhosis; Esophageal Varices; Varice Bleed; Gastric Varices Bleeding; Liver Diseases

• Registration Number: NCT03438916
• Lead Sponsor: Hvidovre University Hospital

Brief Summary

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.

Detailed Description

MR-elastography and Phase Contrast MRI compared to LVC

Study Timeline

• Study Start: 2017-04-01
• Study First Submitted: 2018-02-10
• Study First Submitted QC: 2018-02-18
• Study First Posted: 2018-02-20
• Primary Completion: 2020-12-08
• Study Completion: 2020-12-08
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-13
• Last Update Posted: 2023-03-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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	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

Secondary Outcome Measures

Name	Time	Method
MR-elastography	after 20 minutes	To assess the liver and spleen stiffness (kPa) with MRE before and after intraveneus NSBB administration

Trial Locations

Locations (1)

Centre of Gastroenterology, Dept. of medicine. Hvidovre University Hospital; 🇩🇰 Hvidovre, Denmark