Biopsy, Fine-needleNCT03622229
EUS-FNB for Solid Pancreatic Lesions: Side-fenestrated Vs Fork-tip Needle
A study testing Histologic evaluation in people with Biopsy, Fine-needle and Pancreatic Neoplasm, run by Azienda Ospedaliera Universitaria Integrata Verona at 2 sites in Italy.
Trial summary
Rationale: Until now there are no prospective studies comparing the 22 gauge and 25 gauge side-fenestrated and fork-tip needles. In the present study we will compare the two types of needles in terms of histological yield for the evaluation of solid pancreatic lesions in the absence of rapid on-site evaluation (ROSE). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Biopsy, Fine-needle, Pancreatic Neoplasm
- What is being tested?
- Histologic evaluation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Nov 2018to 30 Aug 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Solid pancreatic mass referred for EUS-guided tissue acquisition.
- Written informed consent.
Who cannot join
- Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma (FFP).
- Cystic lesions even with solid component.
- Previous inclusion in present study.
- Previous histological or cytological diagnosis.
- Pancreatic lesion not seen at EUS.
- Technical impossibility to perform EUS-FNB (for example, for the interposition of vessels).
- Patients in an emergency situation.
- Pregnancy or feeding time.
Trial locations and contacts
2 sites in 1 country.
Italy2 sites
Stefano Francesco Crinò
Verona, 37100
Azienda Ospedaliera Integrata Verona
Verona, 37134
About this study
Official title: Single Center Randomized Clinical Trial to Evaluate the Histological and Diagnostic Accuracy of Two EUS Fine Needles Biopsy for the Diagnosis of Solid Pancreatic Lesions
Rationale: Until now there are no prospective studies comparing the 22 gauge and 25 gauge side-fenestrated and fork-tip needles.
In the present study we will compare the two types of needles in terms of histological yield for the evaluation of solid pancreatic lesions in the absence of rapid on-site evaluation (ROSE). Moreover diagnostic accuracy and the number of passes necessary to achieve the maximum diagnostic and histological yield, and safety will be investigated.
Read more
Objectives: To evaluate and compare the histologic retrieval rate of two different EUS-FNB needles of the same caliber (22 or 25 gauge). The passes will be 3 for each patient.
Study design: Randomized monocentric trial. Study population: Patients ≥18 years old, referred for EUS-guided tissue sampling of a solid pancreatic mass.
Intervention: EUS-guided tissue acquisition by mean EUS-FNB, using one of the following FNB needles: side-fenestrated 22 gauge, side-fenestrated 25 gauge, fork-tip 22 gauge or fork-tip 25 gauge.
Main study parameters/endpoints: The main endpoint is the histologic yield (defined as the percentage of a tissue core of at least 550 micron at the greatest axis), obtained at each of the 3 needle passes. Secondary endpoints include: i) safety; ii) concordance between macroscopic on-site evaluation (MOSE) and histopathological evaluation ; iii) Accuracy using 1, 2 or 3 passes.
Read the detailed description
Endoscopic ultrasound (EUS) has become an essential procedure in the last decade for evaluation of focal pancreatic lesions and for tissue acquisition for diagnostic purposes. In these patients the endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and, more recently, the introduction of EUS fine needle biopsy (EUS-FNB), is a safe instrument, with high sensitivity (75-98 %) and specificity (71-100%).
The obtaining of bioptic tissue samples reduces the need for rapid on site-evaluation (ROSE) and allows an easier interpretation of the diagnosis even by non-expert pathologist. It also makes possible to perform ancillary investigations such as immunohistochemical, often useful for the differential diagnosis.
Two different EUS-FNB needles are available: the side-fenestrated reverse bevel and the fork-tip forward-acquiring". Both are available in 25, 22 and 19 gauge. The 22 gauge is the most commonly used since it combines the ease of use of small-sized caliber with the advantages of larger sized needles. The 25 gauge is universally recognized as the most manageable and flexible needle and is preferred when the lesion is small (<20mm) or is in "difficult" conditions (lesion localized to the uncinate process or to distal tail, lesion distant from the transducer > 15mm, need to cross > 1cm of healthy pancreas, angled position of the instrument).
There are no prospective studies comparing the 22 and 25 gauge side-fenestrated and fork-tip needles. We therefore propose a prospective randomized study, to compare the two types of needles in terms of histologic and diagnostic yield, number of passes necessary to reach it in solid pancreatic lesions, in the absence of ROSE.
This is a randomized single center trial with two parallel arms in a (1:1) ratio. Consecutive patients with solid pancreatic masses and an indication to perform EUS-guided tissue acquisition will be evaluated and, if eligible, will be enrolled into the study. Randomization will take place after the lesion will have been visualized with EUS and the patient will be found suitable for inclusion.
The choice of needle gauge (22 or 25 gauge) will be at the discretion of the endosonographer in relation to the difficulty/risk of the procedure; therefore, two randomization lists will be drawn up, (one for the 22 gauge and one for the 25 gauge).
The choice of the needle gauge will be done before randomization so that the choice of the needle does not create bias in the results. The pathologist will be blinded to the needle caliber and type.
The sample size has been calculated for the primary outcome (histologic retrieval rate) using a group sequential design to define a proper interim analysis after at least 50% enrolment. The histologic yield of the two needle types can be summarized as follows:
22 gauge: 77% and 92% for the side-fenestrated and the fork-tip, respectively. 25 gauge: 60.5% and 85% for the side-fenestrated and the fork-tip, respectively.
With a type I error α of 5% and a power 1 - β of 80%, the total required sample size amounts to 330 patients (210 patients for 22G group and 120 patients for 25G group). Considering that 18% of patients must be added to counteract the estimated and lost drop-out rate at follow-up, overall 362 patients will be needed (196 patients for the 22G group and 112 patients for the 25G group).
Based on sample size calculation the two lists will consist in 24 blocks of 8 patients and 1 block of 4 patients for the 22G group and 14 blocks of 8 patients for the 25G group.
- Conditions
- Biopsy, Fine-needle, Pancreatic Neoplasm
- Being tested
- Histologic evaluation
- Keywords
- pancreatic cancer, endoscopic ultrasound, fine needle biopsy
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Histologic evaluationDiagnostic test
Samples collected by EUS-FNB without ROSE will be processed as histologic samples
| Study group | Role | What they receive |
|---|---|---|
| EUS-FNB with side-fenestrated needle | Active comparator | Before randomization, the endosonographer chooses the needle gauge to perform biopsy preferring the 25 gauge caliber for "difficult" lesions. The needle advances inside the lesion and the operator will perform some needle movements back and forth into the lesion while slowly withdrawn the stylet (slow-pull technique). If possible the direction of the needle inside the lesion will be changed during the movements (fanning technique) to sample different areas of the lesion. Three needle passes will be performed and the material acquired at each pass will be placed directly in formalin in a single vial.
Diagnostic Test: Histologic evaluation Receives: Diagnostic Test: Histologic evaluation |
| EUS-FNB with fork-tip needle | Active comparator | Intervention: like above.
Diagnostic Test: Histologic evaluation. Receives: Diagnostic Test: Histologic evaluation |
What is being measured
The primary outcome is the main question the study is designed to answer.
EUS-FNB procurement yield of tissue "core" using two different FNB needles.
Procurement percentage of a "core" (defined as a piece of tissue at least 550 micron in the greatest axis) in the two arms.
Measured: 6 months
Secondary outcomes (8)
Diagnostic accuracy.
Diagnostic accuracy (defined as the ratio between the sum of true positive and true negative values divided by the number of lesions) will be calculated for each study arm.
Measured: 6 months
Diagnostic accuracy according to the number of needle passes
Diagnostic accuracy (defined as the ratio between the sum of true positive and true negative values divided by the number of lesions) will be calculated after 1, 2 or 3 needle passes in the two study arms.
Measured: 6 months
Histologic retrieval rate according to the number of needle passes
Percentage of tissue core (defined as an intact piece of tissue of at least 550 micron in the greatest axis) will be calculated after 1, 2 or 3 needle passes in the two study arms.
Measured: 6 months
Procedure related adverse events
Percentage of intra-procedural and post-procedural adverse events in the 2 arms (e.g haemorrhage, perforation, pancreatitis) will be compared.
Measured: 6 months
Procedure related serious adverse events.
Percentage of serous adverse events in the 2 arms (e.g long hospitalization, disability, death) will be compared.
Measured: 6 months
Samples tissue integrity
Tissue integrity will be evaluated by attributing a score from zero to 6 (6 represents the better outcome), according to the following score system:
0=Insufficient material for interpretation. 1=Sufficient material for limited cytological interpretation; probably not representative. 2=Sufficient material for adequate cytological interpretation. 3=Sufficient material for low quality histological interpretation (tissue fragments < 550 micron in greatest axis). 4=Sufficient material for good quality histological interpretation (1 to 5 cores > 550 micron in greatest axis). 5=Sufficient material for high quality histological interpretation (6 to 10 cores > 550 micron in greatest axis). 6=Sufficient material for excellent quality histological interpretation (more than 10 cores > 550 micron in greatest axis or total tissue length > 5.500 micron);
Measured: 6 months
Samples blood contamination
Blood contamination will be evaluated by attributing a score from 0 to 3 (3 represents the better outcome), according to the following score system:
0=Only blood; 1=Much blood contamination, surface area > 50 % of the slide; 2=Medium blood contamination, surface area 25-50 % of the slide; 3=Little blood contamination, surface area < 25 % of slide.
Measured: 6 months
Macroscopic on-site evaluation (MOSE)
Concordance between presence of a core at Macroscopic on-site evaluation (MOSE) and presence of core at histopathological evaluation.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2018
- Study start1 Nov 2018
- Primary completion13 Dec 2019
- Study completion30 Aug 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Biopsy, Fine-needleStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Azienda Ospedaliera Universitaria Integrata Verona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefano Francesco Crinò, MD, Azienda Ospedaliera Universitaria Integrata Verona
- Investigators
- Stefano Francesco Crinò, Principal investigator, Azienda Ospedaliera Integrata Verona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03622229
- Sponsor's protocol ID
- 1823CESC
- Status last verified
- Jan 2021
- First submitted
- 6 Jul 2018
- Last updated
- 14 Jan 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Crino SF, Le Grazie M, Manfrin E, Conti Bellocchi MC, Bernardoni L, Granato A, Locatelli F, Parisi A, Di Stefano S, Frulloni L, Larghi A, Gabbrielli A. Randomized trial comparing fork-tip and side-fenestrated needles for EUS-guided fine-needle biopsy of solid pancreatic lesions. Gastrointest Endosc. 2020 Sep;92(3):648-658.e2. doi: 10.1016/j.gie.2020.05.016. Epub 2020 May 17.
PubMed 32433914
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Single Center Randomized Clinical Trial to Evaluate the Histological and Diagnostic Accuracy of Two EUS Fine Needles Biopsy for the Diagnosis of Solid Pancreatic Lesions
- ClinicalTrials.gov ID
- NCT03622229
- Acronym / sponsor ID
- 1823CESC
- Conditions
- Biopsy, Fine-needle, Pancreatic Neoplasm
- Keywords
- pancreatic cancer, endoscopic ultrasound, fine needle biopsy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Azienda Ospedaliera Universitaria Integrata VeronaUniversity, hospital or other
- Study start
- 1 Nov 2018 (actual)
- Primary completion
- 13 Dec 2019 (actual)
- Study completion
- 30 Aug 2020 (actual)
- First posted
- 9 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Until now there are no prospective studies comparing the 22 gauge and 25 gauge side-fenestrated and fork-tip needles.
In the present study we will compare the two types of needles in terms of histological yield for the evaluation of solid pancreatic lesions in the absence of rapid on-site evaluation (ROSE). Moreover diagnostic accuracy and the number of passes necessary to achieve the maximum diagnostic and histological yield, and safety will be investigated.
Objectives: To evaluate and compare the histologic retrieval rate of two different EUS-FNB needles of the same caliber (22 or 25 gauge). The passes will be 3 for each patient.
Study design: Randomized monocentric trial. Study population: Patients ≥18 years old, referred for EUS-guided tissue sampling of a solid pancreatic mass.
Intervention: EUS-guided tissue acquisition by mean EUS-FNB, using one of the following FNB needles: side-fenestrated 22 gauge, side-fenestrated 25 gauge, fork-tip 22 gauge or fork-tip 25 gauge.
Main study parameters/endpoints: The main endpoint is the histologic yield (defined as the percentage of a tissue core of at least 550 micron at the greatest axis), obtained at each of the 3 needle passes. Secondary endpoints include: i) safety; ii) concordance between macroscopic on-site evaluation (MOSE) and histopathological evaluation ; iii) Accuracy using 1, 2 or 3 passes.
Detailed description
Endoscopic ultrasound (EUS) has become an essential procedure in the last decade for evaluation of focal pancreatic lesions and for tissue acquisition for diagnostic purposes. In these patients the endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) and, more recently, the introduction of EUS fine needle biopsy (EUS-FNB), is a safe instrument, with high sensitivity (75-98 %) and specificity (71-100%).
The obtaining of bioptic tissue samples reduces the need for rapid on site-evaluation (ROSE) and allows an easier interpretation of the diagnosis even by non-expert pathologist. It also makes possible to perform ancillary investigations such as immunohistochemical, often useful for the differential diagnosis.
Two different EUS-FNB needles are available: the side-fenestrated reverse bevel and the fork-tip forward-acquiring". Both are available in 25, 22 and 19 gauge. The 22 gauge is the most commonly used since it combines the ease of use of small-sized caliber with the advantages of larger sized needles. The 25 gauge is universally recognized as the most manageable and flexible needle and is preferred when the lesion is small (<20mm) or is in "difficult" conditions (lesion localized to the uncinate process or to distal tail, lesion distant from the transducer > 15mm, need to cross > 1cm of healthy pancreas, angled position of the instrument).
There are no prospective studies comparing the 22 and 25 gauge side-fenestrated and fork-tip needles. We therefore propose a prospective randomized study, to compare the two types of needles in terms of histologic and diagnostic yield, number of passes necessary to reach it in solid pancreatic lesions, in the absence of ROSE.
This is a randomized single center trial with two parallel arms in a (1:1) ratio. Consecutive patients with solid pancreatic masses and an indication to perform EUS-guided tissue acquisition will be evaluated and, if eligible, will be enrolled into the study. Randomization will take place after the lesion will have been visualized with EUS and the patient will be found suitable for inclusion.
The choice of needle gauge (22 or 25 gauge) will be at the discretion of the endosonographer in relation to the difficulty/risk of the procedure; therefore, two randomization lists will be drawn up, (one for the 22 gauge and one for the 25 gauge).
The choice of the needle gauge will be done before randomization so that the choice of the needle does not create bias in the results. The pathologist will be blinded to the needle caliber and type.
The sample size has been calculated for the primary outcome (histologic retrieval rate) using a group sequential design to define a proper interim analysis after at least 50% enrolment. The histologic yield of the two needle types can be summarized as follows:
22 gauge: 77% and 92% for the side-fenestrated and the fork-tip, respectively. 25 gauge: 60.5% and 85% for the side-fenestrated and the fork-tip, respectively.
With a type I error α of 5% and a power 1 - β of 80%, the total required sample size amounts to 330 patients (210 patients for 22G group and 120 patients for 25G group). Considering that 18% of patients must be added to counteract the estimated and lost drop-out rate at follow-up, overall 362 patients will be needed (196 patients for the 22G group and 112 patients for the 25G group).
Based on sample size calculation the two lists will consist in 24 blocks of 8 patients and 1 block of 4 patients for the 22G group and 14 blocks of 8 patients for the 25G group.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| EUS-FNB with side-fenestrated needle | Active comparator | Diagnostic Test: Histologic evaluationBefore randomization, the endosonographer chooses the needle gauge to perform biopsy preferring the 25 gauge caliber for "difficult" lesions. The needle advances inside the lesion and the operator will perform some needle movements back and forth into the lesion while slowly withdrawn the stylet (slow-pull technique). If possible the direction of the needle inside the lesion will be changed during the movements (fanning technique) to sample different areas of the lesion. Three needle passes will be performed and the material acquired at each pass will be placed directly in formalin in a single vial. Diagnostic Test: Histologic evaluation |
| EUS-FNB with fork-tip needle | Active comparator | Diagnostic Test: Histologic evaluationIntervention: like above. Diagnostic Test: Histologic evaluation. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Solid pancreatic mass referred for EUS-guided tissue acquisition.
- Written informed consent.
Key exclusion criteria (8 listed)
- Known bleeding disorder that cannot be sufficiently corrected with co-fact or fresh frozen plasma (FFP).
- Cystic lesions even with solid component.
- Previous inclusion in present study.
- Previous histological or cytological diagnosis.
- Pancreatic lesion not seen at EUS.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Histologic evaluationSamples collected by EUS-FNB without ROSE will be processed as histologic samples | Diagnostic test | EUS-FNB with fork-tip needle, EUS-FNB with side-fenestrated needle |
Primary outcome
EUS-FNB procurement yield of tissue "core" using two different FNB needles.
Time frame: 6 months
Procurement percentage of a "core" (defined as a piece of tissue at least 550 micron in the greatest axis) in the two arms.
8 secondary outcomes
Diagnostic accuracy.
Time frame: 6 months
Diagnostic accuracy according to the number of needle passes
Time frame: 6 months
Histologic retrieval rate according to the number of needle passes
Time frame: 6 months
Procedure related adverse events
Time frame: 6 months
Procedure related serious adverse events.
Time frame: 6 months
Samples tissue integrity
Time frame: 6 months
Samples blood contamination
Time frame: 6 months
Macroscopic on-site evaluation (MOSE)
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2021.
- Derived from this study: PubMed 32433914Crino SF, Le Grazie M, Manfrin E, Conti Bellocchi MC, Bernardoni L, Granato A, Locatelli F, Parisi A, Di Stefano S, Frulloni L, Larghi A, Gabbrielli A. Randomized trial comparing fork-tip and side-fenestrated needles for EUS-guided fine-needle biopsy of solid pancreatic lesions. Gastrointest Endosc. 2020 Sep;92(3):648-658.e2. doi: 10.1016/j.gie.2020.05.016. Epub 2020 May 17.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stefano Francesco Crinò principal investigator
Azienda Ospedaliera Integrata Verona
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Histologic evaluation in people with Biopsy, Fine-needle and Pancreatic Neoplasm, run by Azienda Ospedaliera Universitaria Integrata Verona at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
EUS-FNB procurement yield of tissue "core" using two different FNB needles. (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03622229, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2021.