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Trial registered on ANZCTR


Registration number
ACTRN12617001011370
Ethics application status
Approved
Date submitted
11/07/2017
Date registered
14/07/2017
Date last updated
5/11/2018
Date data sharing statement initially provided
5/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of fine needle biopsy (FNB) for endoscopic ultrasound (EUS) guided tissue acquisition of pancreatic masses to negate the need for rapid on-site evaluation: a multi-centre randomized control trial
Scientific title
Diagnostic accuracy of fine needle aspiration (FNA) with 22G EchoTip needle and rapid on-site evaluation (ROSE) versus fine needle biopsy (FNB) with 22G ProCore needle and without ROSE for EUS guided tissue acquisition of pancreatic masses: a multi-centre randomized control trial.
Secondary ID [1] 292417 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Investigation and diagnosis of pancreatic lesions / masses 304003 0
Condition category
Condition code
Oral and Gastrointestinal 303337 303337 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
Evaluation of fine needle biopsy (FNB) for endoscopic ultrasound (EUS) guided tissue acquisition of pancreatic masses to negate the need for rapid on-site evaluation: a multi-centre randomized control trial
Eligible patients will be invited to participate in the trial and provided with the Patient Information Sheet and encouraged to ask questions. Once the patient has agreed to go ahead with the study they will be asked sign the consent form. Consenting patients will be randomized to either group A or group B. The randomization sequence will be determined using a central computerized randomizing program. In both groups, the procedure will be performed at the Department of Gastroenterology, Royal Adelaide Hospital, under deep sedation (Propofol, as determined by patient weight), administered by qualified anaesthetists. After the lesion is evaluated by EUS, the endoscopist will perform the tissue sampling using the most appropriate pathway deemed at the time.
Group A will undergo EUS fine needle aspiration (FNA) with the 22G EchoTip needle. Each pass will undergo rapid on-site evaluation (ROSE) by a trained cytopathologist or cytotechnician (ROSE slides prepared in the endoscopy suite with Papanicolaou stain and the remaining sample to be placed into Hanks solution in order to develop a paraffin embedded cell block). The degree of suction will be determined by the endoscopist and the degree of “bloodiness” of the specimen. The endoscopist will perform passes until the cytopathologist or cytotechnician satisfies the quality of specimen that allow determination of the diagnosis, to a maximum of 7 passes.
Group B will undergo EUS FNB with the 22G ProCore needle without the presence of ROSE. A total of 4 passes will be done per lesion using suction via a 10ml syringe (with the fanning technique done when possible). All aspirated material will be placed in formalin to undergo direct histological processing (filtered through a microcassette, immersed in Ponceau S tinted neutral buffered formalin and processed as standard histological blocks).
All patients will be observed in recovery for a minimum 2 hours following the procedure for any complications.
Trained cytologists and pathologists will assess the final processed samples from each group in order to determine the diagnosis. The diagnostic reports will be stratified into the following categories:
1. Positive for malignancy
2. Suspicious for malignancy
3. Atypia
4. Negative for malignancy
Intervention code [1] 298585 0
Diagnosis / Prognosis
Comparator / control treatment
Patients who assigned to the EUS FNA ROSE group
Control group
Active

Outcomes
Primary outcome [1] 302723 0
To compare the differences in the diagnostic yield between the groups.

This will be determined via 2 methods:
1. Definite histological diagnoses from surgically resected specimens.
2.In the absence of surgical resection, a minimum 24 weeks follow-up will be done. Lesions that resolve spontaneously or do not progress (as seen on imaging) will be considered benign. If lesions progress (enlarge or metastasize) then those lesions will be considered malignant.
Timepoint [1] 302723 0
2 days post procedure diagnoses are made. Differences between groups to be compared once a sufficient patients have been diagnosed, approximately 1 year within commencement of study.
In the absence of surgical resection, a minimum 24 weeks follow-up will be done, and a maximum 48 weeks.
Secondary outcome [1] 336827 0
To compare the differences between tissue characteristics between the needles.

Assessed by trained cytologists and pathologists, the final processed samples from each group in order to determine the diagnosis. The diagnostic reports will be stratified into the following categories:
1. Positive for malignancy
2. Suspicious for malignancy
3. Atypia
4. Negative for malignancy
Timepoint [1] 336827 0
2 days post procedure diagnoses are made. Differences between groups to be compared once a sufficient patients have been diagnosed, approximately 1 year within commencement of study.
Secondary outcome [2] 336828 0
To compare the differences between complication rates in the groups.

Assessed via medical records, monitoring primarily for bleeding, perforation and pancreatitis
Timepoint [2] 336828 0
This outcome is assessed 7 days post procedure via medical records. In the absence of surgical resection, a minimum 24 weeks follow-up will be done, and a maximum 48 weeks.
Secondary outcome [3] 336829 0
To compare the differences between groups for the need to repeat procedure.

Assessed via medical records and with communication with the cytologists and pathologists.
Timepoint [3] 336829 0
Within 2 days post procedure the need for repeat procedure is usually determined. In the absence of surgical resection, a minimum 24 weeks follow-up will be done, and a maximum 48 weeks.
Secondary outcome [4] 336860 0
To compare the procedural time required for both procedures. This outcome is assessed by monitoring and recording time taken during the procedure.
Timepoint [4] 336860 0
Procedure time determined during the procedure. Differences between groups to be compared once sufficient patients have been diagnosed, approximately 1 year within commencement of study.
Secondary outcome [5] 336861 0
To compare time required for specimen processing for both procedures. This outcome is assessed by monitoring and recording time taken during specimen processing.
Timepoint [5] 336861 0
Specimen processing time is determined within 2 days of procedure. Differences between groups to be compared once sufficient patients have been diagnosed, approximately 1 year within commencement of study.
Secondary outcome [6] 336862 0
To compare the time required for diagnosis from both procedures. This outcome is assessed by monitoring and recording time taken to receive diagnosis of patient’s results.
Timepoint [6] 336862 0
Diagnosis time is determined within 2 days of procedure. Differences between groups to be compared once sufficient patients have been diagnosed, approximately 1 year within commencement of study. In the absence of surgical resection, a minimum 24 weeks follow-up will be done.
Lesions that resolve spontaneously or do not progress (as seen on imaging) will be considered benign. If lesions progress (enlarge or metastasize) then those lesions will be considered malignant.

Eligibility
Key inclusion criteria
1. Aged 18 years old or over
2. Patients requiring endoscopic ultrasound and tissue sampling of solid lesions greater than 1cm diameter in the pancreas that are visualized and within the reach of EUS FNA.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pregnant females
2. Uncorrectable coagulation disorder (INR > 1.5)
3. Those with medical co-morbidities that preclude them from sedation (as determined by anaesthetic team)
4. Actively on medications that increase the risk of bleeding from EUS guided tissue acquisition (NOAC, warfarin, combined aspirin and clopidogrel)
5. Those unable to give informed consent

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Randomised controlled 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
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 8511 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 16604 0
5000 - Adelaide

Funding & Sponsors
Funding source category [1] 296966 0
Hospital
Name [1] 296966 0
Royal Adelaide Hospital
Address [1] 296966 0
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country [1] 296966 0
Australia
Primary sponsor type
Hospital
Name
Royal Adelaide Hospital
Address
Department of Gastroenterology and Hepatology,
Royal Adelaide Hospital, North Terrace, Adelaide, SA, 5000
Country
Australia
Secondary sponsor category [1] 295971 0
None
Name [1] 295971 0
N/A
Address [1] 295971 0
N/A
Country [1] 295971 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298171 0
Royal Adelaide Hospital Human Research Ethics Committee
Ethics committee address [1] 298171 0
Ethics committee country [1] 298171 0
Date submitted for ethics approval [1] 298171 0
Approval date [1] 298171 0
23/06/2017
Ethics approval number [1] 298171 0
HREC/17/RAH/57

Summary
Brief summary
Background: Endoscopic ultrasound guided fine needle aspiration (EUS FNA) is a key component for the investigation and diagnosis of solid pancreatic masse. It has a proven track record for being safe with complications and tumour seeding being a rare occurrence. The sensitivity, specificity and diagnostic accuracy for pancreatic lesions in many studies is high and exceeds 85%. Studies aiming to optimize EUS FNA have compared several factors including needle size, the number of needles passes and suction versus slow-pull. Initial studies showed that the use of rapid on-site evaluation (ROSE) had the biggest impact with increased diagnostic accuracy and reduced needle passes. However more recent reports show conflicting results on whether ROSE actually does influence outcome in EUS FNA.

ROSE has historically been performed using FNA needles with cytological assessment. The act of smearing specimens (a necessary step for ROSE) to prepare cytology slides using cell aspirates obtained from FNA needles can be done without difficulty after necessary training and experience.
The fine needle biopsy (FNB) needle (the ProCore needle) was introduced to further improve upon EUS guided tissue sampling. It is designed to collect a larger amount of core sample tissue by having a reverse bevel near the tip. Several studies favour the EUS FNB needle over the classic FNA needle for obtaining more adequate histological specimens with a high diagnostic yield.
Data comparing the performance of EUS FNB without ROSE versus EUS FNA with ROSE is currently lacking. With this in mind, needles that provide histological specimens with an excellent (>95%) diagnostic yield (thus negating the need for ROSE) are the ideal devices for obtaining EUS guided diagnostic tissue. We therefore aim to compare the diagnostic yield of solid pancreatic masses using EUS FNA with ROSE versus EUS FNB without ROSE.
Hypothesis: EUS FNB without ROSE will have equal diagnostic accuracy to EUS FNA with ROSE, hence negating the need for ROSE when EUS guided tissue acquisition is performed with FNB needle for solid pancreatic masses.
Aim: To compare the outcomes of EUS FNA with ROSE versus EUS FNB without ROSE for solid pancreatic masses.
Design: This will be a prospective, multi-centre, randomized control trial involving 600 patients with pancreatic solid mass of more than 1cm. There will be 10 centres participate in the trial, each recruiting 60 patients per hospital. Patients at each site will be randomized to either: Group A, (n=30, total = 300) which will undergo EUS FNA with the standard 22G EchoTip needle with ROSE. Group B (n=30; total=300), which will undergo EUS FNB with the 22G ProCore needle without ROSE.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76218 0
Dr Vinh-An Huu
Address 76218 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000
Country 76218 0
Australia
Phone 76218 0
+61 8 7074 2189
Fax 76218 0
Email 76218 0
Vinh-AnHuu.Phan@sa.gov.au
Contact person for public queries
Name 76219 0
Ms Romina Safaeian
Address 76219 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000
Country 76219 0
Australia
Phone 76219 0
+61 8 7074 2189
Fax 76219 0
Email 76219 0
romina.safaeian@sa.gov.au
Contact person for scientific queries
Name 76220 0
Ms Romina Safaeian
Address 76220 0
Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Port Road, Adelaide, SA, 5000
Country 76220 0
Australia
Phone 76220 0
+61 8 7074 2189
Fax 76220 0
Email 76220 0
romina.safaeian@sa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Investigator is undecided if IPD will be made available, at this stage
What supporting documents are/will be available?
No other documents available
Summary results
No Results