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

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ClinicalTrials.gov Identifier: NCT03438916
Recruitment Status : Recruiting
First Posted : February 20, 2018
Last Update Posted : August 7, 2019
Sponsor:
Information provided by (Responsible Party):
Flemming Bendtsen, 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.


Condition or disease
Portal Hypertension Cirrhosis Esophageal Varices Gastric Varices Bleeding Varice Bleed Liver Diseases Liver Cirrhosis

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Study Type : Observational
Estimated Enrollment : 39 participants
Observational Model: Cohort
Time Perspective: Prospective
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?
Actual Study Start Date : April 1, 2017
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023





Primary Outcome Measures :
  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 [ 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


Secondary Outcome Measures :
  1. MR-elastography [ Time Frame: after 20 minutes ]
    To assess the liver and spleen stiffness (kPa) with MRE before and after intraveneus NSBB administration


Biospecimen Retention:   Samples Without DNA
Standard clinical blood tests and pertinent bioactive substances is measured in blood and urine


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Ages Eligible for Study:   18 Years to 78 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
39 patients with cirrhosis and esophageal varices that require NSBB (propranolol) treatment.
Criteria

Inclusion Criteria:

  • Patients with cirrhosis and esophageal varices that require NSBB treatment
  • Patient of more than 18 and less than 78 years of age
  • Patient with a portal pressure HVPG ≥ 10mmHg

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03438916


Contacts
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Contact: Karen V Danielsen +45 22439449 karen.vagner.danielsen.02@regionh.dk
Contact: Flemming Bendtsen, Professor flemming.bendtsen@regionh.dk

Locations
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Denmark
Centre of Gastroenterology, Dept. of medicine. Hvidovre University Hospital Recruiting
Hvidovre, Denmark, 2650
Contact: Flemming Bendtsen, Professor       flemming.bendtsen@regionh.dk   
Sponsors and Collaborators
Hvidovre University Hospital
Investigators
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Principal Investigator: Flemming Bendtsen, Professor Professor

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Responsible Party: Flemming Bendtsen, Professor, MD, Hvidovre University Hospital
ClinicalTrials.gov Identifier: NCT03438916     History of Changes
Other Study ID Numbers: 16048475
First Posted: February 20, 2018    Key Record Dates
Last Update Posted: August 7, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Flemming Bendtsen, Hvidovre University Hospital:
Non-selective beta-blocker
Pharmacological respons
Magnetic Resonance Imaging
Hemodynamic assessments
Echocardiography
MR-elastography
Propranolol
Liver vein catheterization
Additional relevant MeSH terms:
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Liver Cirrhosis
Liver Diseases
Hypertension, Portal
Esophageal and Gastric Varices
Varicose Veins
Fibrosis
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs