MRI assessment for beta-blockers in portal hypertension

ISRCTN ISRCTN98001632
DOI https://doi.org/10.1186/ISRCTN98001632
Secondary identifying numbers 1.2
Submission date
17/05/2017
Registration date
19/05/2017
Last edited
18/07/2017
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and study aims
Portal hypertension (PHT) is where the blood pressure in the main vein of the liver (the portal vein) becomes too high. If a person has cirrhosis (irreversible scarring of the liver caused by liver disease), blood flow through the portal vein is disrupted, leading to an increase in blood pressure. This can lead to the smaller veins that supply the portal vein bursting, causing bleeds inside the gullet (varices). Non-selective beta-blockers (NSBB) are a type of medication used to treat various conditions including angina (chest pain) and high blood pressure. Long-term treatment with beta-blockers can help to reduce the risk of varicies, but less than one third of patients respond to these drugs and a fifth stop treatment due to side effects. New drugs are emerging that may be more effective and better tolerated. The aim of this study is to find out whether it is possible to develop an effective noninvasive test to monitor the effect of drugs on portal hypertension.

Who can participate?
Adults with liver cirrhosis, who need NSBB treatment for portal hypertension as part of their standard NHS care

What does the study involve?
Participants due to receive NSBB treatment as part of their normal care are randomly allocated to receive treatment with one of two NSBBs. Those in the first group are treated with propranolol and those in the second group are treated with carvedilol (a newer NSBB that is thought to work in a different way). Before starting their treatment and then four weeks later, participants in both groups undergo an MRI scan (a type of body scan that uses strong magnetic fields and radio waves to produce detailed images of the inside of the body) to assess the severity of their liver diseases. In addition, participants also undergo routine laboratory investigations to assess blood flow and general health.

What are the possible benefits and risks of participating?
There are no direct benefits or risks involved with participating.

Where is the study run from?
Royal Infirmary of Edinburgh (UK)

When is the study starting and how long is it expected to run for?
December 2014 to March 2016

Who is funding the study?
Chief Scientist Office (UK)

Who is the main contact?
Dr Jonathan Fallowfield
Jonathan.Fallowfield@ed.ac.uk

Contact information

Dr Jonathan Fallowfield
Scientific

MRC Centre for Inflammation Research
Queens Medical Research Institute
47 Little France Crescent
Edinburgh
EH16 4TJ
United Kingdom

ORCiD logoORCID ID 0000-0002-5741-1471
Phone +44 (0)131 242 6655
Email Jonathan.Fallowfield@ed.ac.uk

Study information

Study designSingle-centre open-label randomised parallel trial
Primary study designInterventional
Secondary study designRandomised parallel trial
Study setting(s)Hospital
Study typeDiagnostic
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleNon-invasive assessment of haemodynamic response to beta-blockers using magnetic resonance imaging in patients with portal hypertension
Study objectivesThe aim of this study is to find out whether it is possible to develop an effective noninvasive test to monitor the effect of drugs on portal hypertension (the major cause of complications and death in liver cirrhosis).
Ethics approval(s)South East Scotland 02 REC, 29/09/2014, ref: 14/SS/1050
Health condition(s) or problem(s) studiedPortal hypertension
InterventionPatients with liver cirrhosis who were about to commence non-selective beta-blocker (NSBB) therapy as part of clinical management of portal hypertension (PHT) are enrolled into the study.

Upon enrolment, information on liver disease aetiology, past medical history, medication and alcohol history, and results of the most recent upper gastrointestinal endoscopy are recorded. Prior to starting NSBB therapy, patients undergo a physical examination and routine laboratory investigations (full blood count, coagulation screen, liver and renal function tests), followed by a baseline research MRI scan (phase-contrast MR angiography, liver and spleen T1 mapping). Liver disease severity is also assessed at baseline according to Model for End Stage Liver Disease (MELD) and Child-Pugh score.

Patients are randomised in a 1:1 ratio to once-daily treatment with carvedilol or modified-release propranolol at an initial dose of 6.25mg or 80mg respectively. Patients’ compliance with medication and adverse event monitoring are assessed at an initial follow-up visit after 1 week of NSBB therapy. Provided that NSBB are tolerated clinically and haemodynamically (resting heart rate (HR) ≥50 beats per minute (b.p.m), systolic blood pressure ≥95 mmHg), the dose is escalated to the clinical target dose of 12.5mg of carvedilol or 160mg of propranolol.

Further treatment compliance and adverse event monitoring takes place by weekly telephone consultations. After 4 weeks, when established on NSBB, the second research MRI scan is performed. An interval of 4 weeks has been chosen as haemodynamic responses to NSBB after chronic use exceed the acute response rate. Consistent with a previous landmark NSBB trial in PHT, treatment is targeted at a resting HR reduction of more than 25% from baseline; this was defined as a clinical haemodynamic response to NSBB (HR responders). Following the study, participants continue taking NSBB and are managed by their existing NHS consultant.
Intervention typeDevice
Pharmaceutical study type(s)
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measureVolumetric blood flow [L/min] in selected blood vessels (proper hepatic artery, portal vein, superior mesenteric artery, superior aorta, inferior aorta, renal arteries and azygous vein) measured by phase-contrast MR angiography at baseline and 4 weeks.
Secondary outcome measuresCorrelation between MRI blood flow measurements and liver disease severity (using MELD and Child-Pugh scores) assessed at baseline and at 4 weeks.
Overall study start date01/12/2014
Completion date31/03/2016

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
Upper age limit80 Years
SexBoth
Target number of participants20
Key inclusion criteria1. Male or female patients aged 18-80 with liver cirrhosis
2. Portal hypertension in whom commencement of beta-blockers is clinically indicated
Key exclusion criteria1. Contraindication to Beta-Blocker therapy (such as moderate to severe asthma)
2. Contraindication to MRI scan
3. Contraindication to administration of gadolinium-based MRI contrast (including eGFR <30mL/min)
4. Concomitant use of other vasoactive drugs (e.g. nitrates, phosphodiesterase inhibitors)
5. Previous TIPSS insertion
6. Portal vein thrombosis
7. Hepatocellular carcinoma
8. Pregnancy or breastfeeding
9. Inability to obtain informed consent (e.g. refusal/overt hepatic encephalopathy)
Date of first enrolment01/01/2015
Date of final enrolment01/03/2016

Locations

Countries of recruitment

  • Scotland
  • United Kingdom

Study participating centre

Royal Infirmary of Edinburgh
51 Little France Drive
Edinburgh
EH16 4SA
United Kingdom

Sponsor information

University of Edinburgh/ACCORD
University/education

Research Governance & QA Office
The Queen's Medical Research Institute
University of Edinburgh
Edinburgh
EH16 4TJ
Scotland
United Kingdom

Website http://accord.scot/
ROR logo "ROR" https://ror.org/01nrxwf90

Funders

Funder type

Government

Chief Scientist Office
Government organisation / Local government
Alternative name(s)
CSO
Location
United Kingdom

Results and Publications

Intention to publish date01/07/2017
Individual participant data (IPD) Intention to shareYes
IPD sharing plan summaryAvailable on request
Publication and dissemination planThe study findings have been submitted for publication in a Special Issue of the Journal Biomed Research International ("Prognostic Assessment and Management of Liver Cirrhosis").
IPD sharing planData from this clinical research study is held by the University of Edinburgh and is available on request by contacting Sheila.Marshall@ed.ac.uk.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/08/2017 Yes No
HRA research summary 28/06/2023 No No

Editorial Notes

18/07/2017: Publication reference added.