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

NCT03438916 | Completed

• 1 other identifier: 16048475
• Study Type: observational
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Non-selective beta-blocker; Pharmacological respons; Magnetic Resonance Imaging; Hemodynamic assessments; Echocardiography; MR-elastography; Propranolol; Liver vein catheterization

Outcome Measures

Primary Outcomes (1)

• 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

  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 Outcomes (1)

• MR-elastography

  after 20 minutes

Eligibility Criteria

• Age: 18 Years - 78 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hvidovre University Hospital: lead

Study Sites (1)

Centre of Gastroenterology, Dept. of medicine. Hvidovre University Hospital

Hvidovre, 2650, Denmark

Location

Related Publications (2)

• Danielsen KV, Nabilou P, Wiese SS, Hove JD, Bendtsen F, Moller S. Effect of beta-blockers on multiple haemodynamics in cirrhosis: A cross-over study by MR-imaging and hepatic vein catheterization. Liver Int. 2023 Oct;43(10):2245-2255. doi: 10.1111/liv.15664. Epub 2023 Jun 30.

  PMID: 37387503 DERIVED

• Danielsen KV, Hove JD, Nabilou P, Yin M, Chen J, Zhao M, Kallemose T, Teisner AS, Siebner HR, Ehman RL, Moller S, Bendtsen F. Using MR elastography to assess portal hypertension and response to beta-blockers in patients with cirrhosis. Liver Int. 2021 Sep;41(9):2149-2158. doi: 10.1111/liv.14981. Epub 2021 Jun 16.

  PMID: 34060714 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Standard clinical blood tests and pertinent bioactive substances is measured in blood and urine

MeSH Terms

Conditions

Hypertension, Portal; Fibrosis; Esophageal and Gastric Varices; Liver Diseases; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Esophageal Diseases; Gastrointestinal Diseases

Study Officials

• Flemming Bendtsen, Professor

  Professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD

Study Record Dates

• First Submitted: February 10, 2018
• First Posted: February 20, 2018
• Study Start: April 1, 2017
• Primary Completion: December 8, 2020
• Study Completion: December 8, 2020
• Last Updated: March 14, 2023

Record last verified: 2023-03

Locations

DK (1)