Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000075785
Ethics application status
Approved
Date submitted
20/10/2021
Date registered
21/01/2022
Date last updated
21/01/2022
Date data sharing statement initially provided
21/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Endoscopic ultrasound (EUS)-guided portal pressure measurement in assessing the effectiveness of suboptimal beta-blocker dosing in primary variceal prophylaxis
Scientific title
EUS-guided portal pressure measurement in assessing the effectiveness of suboptimal beta-blocker dosing for primary variceal prophylaxis in patients with cirrhosis
Secondary ID [1] 305562 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cirrhosis 323958 0
Condition category
Condition code
Oral and Gastrointestinal 321475 321475 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
SUBJECTS
Thirty patients on beta-blockers for primary prophylaxis for variceal bleeding (as per conventional guidelines) but have failed to tolerate up-titration to maximal dose of beta blocker (320mg propranolol daily or carvedilol 12.5mg daily with HR of 50-55bpm).

DESIGN AND PLAN OF STUDY
1.Clinicians identify patients on sub-optimal doses of beta-blocker for variceal bleeding primary variceal banding prophylaxis
2. Patient Consent
3. Enter into study for Endoscopic Ultrasound (EUS) Portal Pressure Gradient (PPG) once patient has had 12 weeks of beta-blocker therapy at current suboptimal dose.

‘EUS-PPGM’ PROCEDURE DETAILS
For the patient, this requires an endoscopic procedure with use of sedation (via anaesthetic support). A forward viewing endoscope is used to record any evidence of oesophageal varices. A linear echoendoscope is then inserted and a 25G fine needle is used to puncture the hepatic vein via a transgastric and transhepatic approach. Three pressure readings will be recorded from the compact manometer. The portal vein will then be punctured also with a 25G fine needle. Three pressure readings will then again be recorded.
It will be performed by a consultant gastroenterologist at Royal Adelaide Hospital.
The procedure takes approximately 30min.

‘LIVER AND SPLENIC TRANSIENT ELASTOGRAPHY’ PROCEDURE DETAILS
This is a non-invasive test and can be performed in clinic or bedside.
The patient lies in supine position, and an ultrasound-like probe is placed over the liver and spleen. Multiple recordings will be taken for liver stiffness and splenic stiffness.
It is performed by either a liver nurse trained in fibroscans, gastroenterology registrar or consultant gastroenterologist.
This will be performed prior to beta-blocker commencement and 6 months post.
The test takes approximately 10-15 minutes.

The overall duration of the study participation including follow-up is 6 months.
Intervention code [1] 321994 0
Diagnosis / Prognosis
Intervention code [2] 322482 0
Early Detection / Screening
Comparator / control treatment
No control
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329297 0
Identify the proportion of patients on suboptimal beta-blocker dosing based on current recommendations (heart rate, HR, >>55bpm, dose<320mg daily propranolol or <12.5mg daily carvedilol) who have adequate portal pressure control. This is assessed by EUS-PPGM measurement.
Timepoint [1] 329297 0
EUS-PPG measurement is assessed after 3 months of trial involvement/beta-blocker therapy.
Primary outcome [2] 330082 0
Identify the proportion of patients on suboptimal beta-blocker dosing based on current recommendations (heart rate, HR, >>55bpm, dose<320mg daily propranolol or <12.5mg daily carvedilol) who do not require alternative treatment (variceal banding regimen). This is also assessed by EUS-PPGM measurement and by referring to patient medical records. An adequate portal pressure gradient measurement of less than 12mmHg suggests no variceal banding, whilst a measurement of 12mmHg or more suggests variceal banding is required.
Timepoint [2] 330082 0
EUS-PPG measurement is assessed after 3 months of trial involvement/beta-blocker therapy.
Secondary outcome [1] 402047 0
Accuracy of non-invasive testing (liver transient elastography – “Fibroscan”) to assess portal hypertension in response to beta-blocker use. Accuracy determined by comparison to EUS-PPGM for sensitivity and specificity.
Timepoint [1] 402047 0
Fibroscan measurement is assessed after 6 months of trial involvement/beta-blocker therapy.
Secondary outcome [2] 404810 0
Accuracy of non-invasive testing (splenic transient elastography) to assess portal hypertension in response to beta-blocker use.
Timepoint [2] 404810 0
Transient elastography measurement is assessed after 6 months of trial involvement/beta-blocker therapy. Accuracy determined by comparison to EUS-PPGM for sensitivity and specificity.

Eligibility
Key inclusion criteria
1 - Ability to give informed consent
2 - Patient with Child A or B cirrhosis - on suboptimal doses of a beta-blocker for variceal primary prophylaxis:
(i) HR > 55bpm
(ii) Propranolol dose < 320mg daily but >= 80mg daily or Carvedilol < 12.5mg daily but >= 6.25mg daily
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1 - Ischaemic heart disease or congestive cardiac failure
2 - Concurrent diagnosis of hepatocellular cancer
3 - Pregnant or breastfeeding women
4 - Creatinine clearance <60 mL/min
5 - Those whom investigators believe are unlikely to have more than 12 month’s life expectancy

Study design
Purpose
Screening
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/02/2022
Actual
Date of last participant enrolment
Anticipated
1/02/2024
Actual
Date of last data collection
Anticipated
1/08/2024
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 20804 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 35623 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 309926 0
Hospital
Name [1] 309926 0
Royal Adelaide Hospital
Country [1] 309926 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Port Road,
Adelaide,
SA, 5000
Country
Australia
Secondary sponsor category [1] 310957 0
None
Name [1] 310957 0
Address [1] 310957 0
Country [1] 310957 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309645 0
The Central Adelaide Local Health Network Human Research Ethics Committee (CALHN HREC)
Ethics committee address [1] 309645 0
Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Ethics committee country [1] 309645 0
Australia
Date submitted for ethics approval [1] 309645 0
Approval date [1] 309645 0
14/10/2021
Ethics approval number [1] 309645 0
2021/HRE00226

Summary
Brief summary
This study is looking to assess whether alternative treatment to prevent variceal bleeding (variceal banding involving multiple endoscopic procedures) is required if you are on a suboptimal dose of a beta-blocker (Propranolol or Carvedilol); a medication that reduces your heart rate and blood pressure, with the aim of reducing the pressure gradient in the liver. Suboptimal dose suggests this is not the highest dose possible reaching the target of a heart rate less than 60. Reasons for being unable to increase the dose may include side effects such as low blood pressure. The aim of the medication is to reduce portal hypertension (portal vein pressure gradient in the liver, causing higher risk of varices and bleeding). If your portal pressure gradient measurement is adequate (<12mmHg) then you would not require alternative prophylaxis with variceal banding.

The aim of this study is to assess the effectiveness of suboptimal doses of beta-blockers in patients unable to tolerate higher doses. Liver inflammation and pressure can be assessed through blood tests, ultrasound and liver elastography (fibroscan) as well as splenic elastography, all of which are non-invasive however these investigations do not measure portal pressure gradient. We are doing this study in the hope that we can optimise treatment management of patients with cirrhosis.

Our overall hypothesis is that directly measuring portal pressure gradient via endoscopic ultrasound (EUS-PPG) can identify patients on suboptimal doses of beta-blockers who do or do not require variceal band ligation for primary prophylaxis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 114886 0
Dr Amanda Lim
Address 114886 0
Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country 114886 0
Australia
Phone 114886 0
+61 8 7074 2188
Fax 114886 0
Email 114886 0
amanda.lim@sa.gov.au
Contact person for public queries
Name 114887 0
Mrs Romina Safaeian
Address 114887 0
Department of Gastroenterology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country 114887 0
Australia
Phone 114887 0
+61 8 7074 2189
Fax 114887 0
Email 114887 0
romina.safaeian@sa.gov.au
Contact person for scientific queries
Name 114888 0
Mrs Romina Safaeian
Address 114888 0
Department of Gastroenterology, Royal Adelaide Hospital, Port Road, Adelaide, Sa 5000
Country 114888 0
Australia
Phone 114888 0
+61 8 7074 2189
Fax 114888 0
Email 114888 0
romina.safaeian@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No plans to share individual participant data


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.