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

Liver Cirrhosis Clinical Trial

Official title:

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?

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03438916
• Other study ID #: 16048475
• Status: Completed
• Start date: April 1, 2017
• Est. completion date: December 8, 2020

Study information

• Verified date: March 2023
• Source: Hvidovre University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

MR-elastography and Phase Contrast MRI compared to LVC

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 8, 2020
• Est. primary completion date: December 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 78 Years

Eligibility

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

Related Conditions & MeSH terms

• Cirrhosis
• Esophageal and Gastric Varices
• Esophageal Varices
• Fibrosis
• Gastric Varices Bleeding
• Hypertension, Portal
• Liver Cirrhosis
• Liver Diseases
• Portal Hypertension
• Varice Bleed
• Varicose Veins

Locations

Country	Name	City	State
Denmark	Centre of Gastroenterology, Dept. of medicine. Hvidovre University Hospital	Hvidovre

Sponsors (1)

Lead Sponsor	Collaborator
Hvidovre University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	MR-elastography	To assess the liver and spleen stiffness (kPa) with MRE before and after intraveneus NSBB administration	after 20 minutes