Trial Review

Technical difficulties have been reported by some users of the search function and is being investigated by technical staff. Thank you for your patience and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12621000464864
Ethics application status
Approved
Date submitted
16/02/2021
Date registered
20/04/2021
Date last updated
20/04/2021
Date data sharing statement initially provided
20/04/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Endoscopic ultrasound guided portal pressure measurement to predict the outcome of liver resection
Scientific title
Comparison of endoscopic ultrasound-guided portal pressure measurement and transjugular hepatic venous pressure gradient measurement as predictors of post-operative outcomes in patients undergoing abdominal surgery/liver resection.
Secondary ID [1] 303484 0
None
Universal Trial Number (UTN)
Trial acronym
EUS PPGM
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Portal Hypertension 320801 0
Liver Cirrhosis 320802 0
Condition category
Condition code
Oral and Gastrointestinal 318624 318624 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All subjects will have Endoscopic Ultrasound-guided Portal Pressure Gradient Measurement (EUS PPGM) and Transjugular Hepatic Venous Pressure Gradient (TJ-HVPG) assessment within 4 weeks of surgery. Procedural details as well as adverse events related to the procedures will be collected immediately after, 24 hours after and 7 days after the procedure.

EUS-PPGM technique:
The EUS-PPGM this will be performed by a gastroenterologist.
Transjugular pressure gradient measurement will be performed by a radiologist.
- the duration of EUS-PPGM- measurement of hepatic vein will take about 8 minutes, measurement of portal vein approximately 8 minutes, procedure time 15 minutes including insertion of echoendoscope
The apparatus for EUS-PPGM will comprise of a linear echoendoscope, a 25G FNA needle, and a compact manometer with non-compressible tubing (Cook Medical, Bloomington, IN). The tubing will be connected by a luer lock to the distal port of the manometer, while the heparinised saline will be connected to the proximal port. The end of the tubing is connected through a luer lock to the inlet of the 25G needle.
First a forward viewing endoscope will be inserted to document any endoscopic evidence of varices (including size and presence of red wale marks) as well as portal hypertensive gastropathy.
Prior to echoendoscope insertion, the manometer will be zeroed at the midaxillary line of the patient. The hepatic vein (HV) measurement will be conducted first. Doppler flow will be used to confirm the typical multiphasic waveform of hepatic venous flow. Using the 25G FNA needle, a transgastric transhepatic approach is used to puncture the HV. Approximately 1 mL of heparinised saline will be used to flush the needle which is visible on EUS to confirm good position within the vessel. After the initial rise in pressure reading as a result of flushing, the manometer reading will equilibrate at a steady pressure, which will then be measured three times. The mean of these three pressures is then considered the HV pressure. The FNA needle is then withdrawn from the vein into the liver parenchyma, and then back into the needle sheath. The needle tract within the liver parenchyma will be observed with Doppler flow on to ensure there is no flow within the needle tract.
The portal vein (PV) measurement will conducted next. The umbilical portion of the left portal vein will be targeted, and Doppler flow will then be used to confirm the typical venous hum of portal venous flow. Using the 25G FNA needle, a transgastric transhepatic approach is used to puncture the PV. The procedure that follows is the same as what would have been performed for the HV. Three readings will be taken, the mean of which is considered the PV pressure. The patient is recovered in a similar manner to a routine diagnostic EUS with FNA, and postprocedural antibiotics are usually given for 5 days postprocedure.

TJ HVPG measurement technique:

We will use the standard technique. Under local anaesthesia and light sedation, a venous catheter introducer sheath will be placed in the right jugular vein, antecubital vein or femoral vein under ultrasound guidance using the Seldinger technique. Under fluoroscopy, a balloon-tipped catheter will be advanced into a main HV. The Free Hepatic Venous Pressure (FHVP) will then be measured with the tip of the catheter in the HV at 2 – 4 cm from its opening into the inferior vena cava. The balloon of the catheter will be inflated to occlude the HV, and occlusion will be confirmed by injection of 5 mL of contrast dye. The measurement of the WHVP will then follow. Each of the WHVP and FHVP measurements will be taken in triplicate, and the mean FHVP will be subtracted from the WHVP to calculate the HVPG.

In terms of monitoring adherence to the intervention, this is only required during the procedure to ensure that it was performed. Procedural details are documented and any adverse events related to the procedures will be collected after 24 hours and 7 days after the procedure.
Intervention code [1] 319774 0
Diagnosis / Prognosis
Comparator / control treatment
Transjugular Hepatic Venous Pressure Gradient technique.
Conducted by radiologist, duration 20-30minutes
WHVP= wedged hepatic venous pressure
Control group
Active

Outcomes
Primary outcome [1] 326581 0
To compare the efficacy between EUS-PPGM and TJ-HVPG measurements. The accuracy of the EUS-PPG in predicting Post hepatectomy liver failure will be assessed by measuring the area under the receiver operating characteristics (AUROC) curve, and differences between AUROCs will be compared using the Hanley-McNeil method. Post-operative liver dysfunction is define as:
(i) serum bilirubin level > 5 mg/dL (> 85.5 umol/L) on or after postoperative day 5; (ii) coagulopathy (INR > 2.0 associated with haemorrhagic complications requiring transfusion); (iii) hepatic encephalopathy; and (iv) abdominal ascites (drainage volumes more than 500 mL/day after day 3).
Timepoint [1] 326581 0
Procedural details will be collected immediately after procedure, and within 24 hours and 7 days post-procedure.
Secondary outcome [1] 391963 0
To compare the safety between EUS-PPGM and TJ hepatic venous pressure gradient measurements. This will include data on intraprocedural or postprocedural complications such as bleeding, perforation, pain, infection, need for transfusion, and length of hospital stay. The data will be collected from electronic medical records and hospital records.
Timepoint [1] 391963 0
Details will be collected immediately after procedure, 24 hours post procedure and/or following discharge from hospital.
Secondary outcome [2] 394035 0
To compare cost differences between EUS PPGM and TJ HVPG technique approaches. Costs will be assessed via hospital medical records, and by calculating the differences between the resources used.
Timepoint [2] 394035 0
This will be assessed within 48 hours following procedure.
Secondary outcome [3] 394036 0
90-day mortality of participant.
Timepoint [3] 394036 0
This will be assessed at 90 day follow up with investigator following their procedure.

Eligibility
Key inclusion criteria
1) Patients (with or without cirrhosis) who are recommended for liver resection or liver transplant
2) Patients with cirrhosis who are recommended to undergo abdominal surgery
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) International Normalised Ratio (INR) > 1.6
2) Significant ascites
3) Child-Pugh C severity of cirrhosis
4) Presence of large gastric varices or periportal collateral vessels that prevent EUS approach to the hepatic and/or portal vasculature

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 18735 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 33179 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 307902 0
Hospital
Name [1] 307902 0
Royal Adelaide Hospital
Country [1] 307902 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Port Road, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 308616 0
None
Name [1] 308616 0
Address [1] 308616 0
Country [1] 308616 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 307899 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 307899 0
Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Ethics committee country [1] 307899 0
Australia
Date submitted for ethics approval [1] 307899 0
Approval date [1] 307899 0
28/01/2021
Ethics approval number [1] 307899 0

Summary
Brief summary
The study is looking for participants that are required to have abdominal surgery, liver resection, or liver transplantation. Portal hypertension is an increase in blood pressure in the portal vein; the blood vessel that carries blood within the gastrointestinal tract to the liver. Portal hypertension is a condition that is present in individuals with cirrhosis of the liver and other liver diseases, and assessing the degree of this condition is important for prognosis, risk evaluating, and to guide appropriate treatment. This is done by calculating a portal pressure measurement.

The current gold standard for measuring portal hypertension is the ‘Transvenous technique’; however, this is a technically limiting procedure with potential complications, and may only provide indirect measurements of portal pressure.

We aim to assess the safety and efficacy of measuring portal pressure via an ‘endoscopic ultrasound technique’ (EUS). Compared to the Transvenous approach, this method is new but is deemed relatively safer and more accurate. We are particularly interested in comparing the clinical outcomes of the two techniques, and to determine that the EUS approach for measuring portal hypertension is much more useful in predicting surgical and survival outcomes for liver disease patients.
The study will not only determine the usefulness and safety profile of the EUS portal pressure measurement, but could also open up a whole new diagnostic approach for the majority of patients with liver diseases.

We hypothesise that: (i) EUS technique for portal pressure measurement can predict clinical outcomes and survival in cirrhotic patients who undergo abdominal surgery, liver resection or liver transplant; and (ii) EUS technique for portal pressure measurement is safe and feasible.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 108870 0
Dr Amanda Lim
Address 108870 0
Department of Gastroenterology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country 108870 0
Australia
Phone 108870 0
+61 8 7074 2189
Fax 108870 0
+61 8 7074 6192
Email 108870 0
amanda.lim@sa.gov.au
Contact person for public queries
Name 108871 0
Mrs Romina Safaeian
Address 108871 0
Department of Gastroenterology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country 108871 0
Australia
Phone 108871 0
+61 8 7074 2189
Fax 108871 0
+61 8 7074 6192
Email 108871 0
romina.safaeian@sa.gov.au
Contact person for scientific queries
Name 108872 0
Mrs Romina Safaeian
Address 108872 0
Department of Gastroenterology, Royal Adelaide Hospital, Port Road, Adelaide, SA 5000
Country 108872 0
Australia
Phone 108872 0
+61 8 7074 2189
Fax 108872 0
+61 8 7074 6192
Email 108872 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
Ethics approval was not obtained to make IPD available. Individual information will be de-identified and will not be disclosed to the public.


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.