Mediastinal LymphadenopathyNCT04200105
EBUS-TBNA vs Acquire TBNB
A study testing EBUS-TBNA and Acquire TBNB in people with Mediastinal Lymphadenopathy, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
This study aims to determine whether a new type of needle used for sampling lymph nodes (glands) around the airways of the lung, during a procedure called an endobronchial ultrasound (EBUS, provides more or better quality tissue to allow a definite diagnosis to be made than with the current standard sampling needle. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mediastinal Lymphadenopathy
- What is being tested?
- EBUS-TBNA and Acquire TBNB
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 250 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 2 Mar 2020to 1 Aug 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Scheduled for EBUS-TBNA as part of clinical care
- Lymph node size ≥5mm on CT scan
- Age > 18 years
- Written informed consent
Who cannot join
- Contraindication to needle biopsy (e.g. coagulopathy, anticoagulation, thrombocytopenia, other bleeding diathesis)
- Inability to obtain informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA) Versus the Endobronchial Ultrasound Transbronchial Needle Biopsy Using the Acquire Needle in the Assessment of Mediastinal and Hilar Lymphadenopathy: a Randomised Trial
This study aims to determine whether a new type of needle used for sampling lymph nodes (glands) around the airways of the lung, during a procedure called an endobronchial ultrasound (EBUS, provides more or better quality tissue to allow a definite diagnosis to be made than with the current standard sampling needle. Two hundred and fifty patients will be randomised to procedures using either the new or standard needle, and the results compared.
Read the detailed description
The causes of mediastinal lymphadenopathy include infection, reactive lymphadenopathy, granulomatous disorders, and malignancy (metastases from various primaries, lymphoma, thymoma, neurogenic tumours). Radiological appearances are usually inadequate at providing a definitive diagnosis. In granulomatous disorders such as sarcoidosis as well as certain infections including tuberculosis, there is frequently mediastinal or hilar lymph node involvement without evidence of disease activity in other organs or lymph node groups. In malignancy, the metastatic involvement of lymph nodes has important prognostic significance. However, lymph node enlargement as seen on computerised tomography (CT) scanning is a poor predictor of disease involvement, and positron emission tomography (PET) of the mediastinum has a 10-15% false positive rate. Adequate mediastinal lymph node sampling is therefore essential in order to reach a definitive diagnosis and obtain satisfactory staging information.
Mediastinal nodal sampling has traditionally been performed using invasive surgical techniques which carry significant morbidity and mortality. These procedures (cervical mediastinoscopy, anterior mediastinotomy) require general anaesthesia and a hospital inpatient stay. Some patients with significant comorbidities are therefore not considered for these procedures as they are deemed unfit for anaesthesia. Safer, less invasive, and more cost-effective procedures using endoscopic ultrasonography to guide needle aspiration of mediastinal lymph nodes have been developed. Endobronchial ultrasound (EBUS) used to guide transbronchial needle aspiration (TBNA) of mediastinal masses has, in a matter of a few years, established itself firmly within the diagnostic and staging algorithm for lung cancer, and also in the diagnosis of other causes of mediastinal and hilar lymphadenopathy such as sarcoidosis and tuberculosis. A wide range of studies has demonstrated the effectiveness and safety of this technique, with various studies reporting sensitivities of between 67% and 92%3.
EBUS-guided needle aspirates performed with 22 gauge needles yield cytological specimens which are often inadequate at providing a firm diagnosis, or at confidently excluding other malignancies such as lymphoma. Immunohistochemistry and mutational analysis are today playing a more important role in the treatment of lung cancer. There is an increasing need for larger tissue samples and ideally biopsy material to enable advanced histopathological examination of specimens. For example, a substantial percentage of lung cancers express cell surface epidermal growth factor receptors (EGFRs). Small molecules designed to inhibit the tyrosine kinase (TK) domain of the EGFR, such as gefitinib and erlotinib, have demonstrated biologic and clinical responses in patients with mutations within the EGFR-TK domain. These TK inhibitors are now an important component of the armamentarium of the thoracic oncologist in the treatment of lung cancer. It has therefore become essential to establish the EGFR mutation status of lung cancers before consideration of treatment. Mutations of the KRAS gene in lung cancer patients have been shown to confer resistance to both erlotinib and gefitinib, adding to the importance of testing tissue samples for these mutations as well. In the past, tests for EGFR and KRAS gene mutations could only be performed on block tumours post resection, however advances in molecular biology in recent years have led to the ability to test small biopsy specimens for such mutations by polymerase chain reaction (PCR) analysis, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). EBUS-TBNA, however, can only provide needle aspirates. These can provide samples adequate for cytological assessment, but do not always contain sufficient material to enable the formation of a cell block, thereby precluding histological assessment. Larger sized core tissue biopsy specimens are therefore likely to help in the histopathological assessment of lung cancer, and also in the diagnosis of sarcoidosis, lymphoma and other causes of mediastinal lymphadenopathy. This is likely to become even more important in the future as new clinically relevant genetic mutations are identified, and appropriate tests developed.
A novel transbronchial needle has been developed. This franseen needle has a crown tipped needle with three symmetrical cutting heels placed in a circumferential pattern designed with the intent to capture more tissue (figure 1). This needle tip was originally designed for use in interventional radiology, and is now the one of the leading designs used in endoscopic ultrasound of the gastrointestinal tract. This new needle can be passed down an EBUS scope and can hypothetically circumvent the deficiencies of EBUS-TBNA highlighted above by providing greater tissue volume for histological assessment and any subsequent molecular and genetic testing.
- Conditions
- Mediastinal Lymphadenopathy
- Being tested
- EBUS-TBNA, Acquire TBNB
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EBUS-TBNADevice
Mediastinal and hilar lymph node sampling using a standard 22G EBUS needle
Acquire TBNBDevice
Mediastinal and hilar lymph node sampling using the Acquire TBNB needle
| Study group | Role | What they receive |
|---|---|---|
| EBUS TBNA | Active comparator | Patients will undergo a standard EBUS examination, with sampling using a standard 22G EBUS needle. Receives: Device: EBUS-TBNA |
| Acquire TBNB | Experimental | Patients will undergo a standard EBUS examination, with sampling using an Acquire TBNB needle. Receives: Device: Acquire TBNB |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference in cell volume of cancer or other diagnostic tissue obtained between the two study arms
Measured: 1 week
Secondary outcomes (7)
The difference between the two study arms in the percentage of lymph nodes sampled where enough tissue is obtained for complete immunohistochemical and genetic mutation analysis.
Measured: 1 month
The difference between the two study arms in the amount of DNA obtained.
Measured: 1 month
The difference in complication rates between the two study arms.
Measured: 1 month
The difference between the two study arms in yield (quantity of diagnostic material) in patients ultimately diagnosed with sarcoidosis.
Measured: 1 month
The difference between the two study arms in yield (quantity of diagnostic material) in patients ultimately diagnosed with lymphoma.
Measured: 1 month
The difference in sensitivity for detecting sarcoidosis between the two study arms.
Measured: 1 month
The difference in sensitivity for detecting lymphoma between the two study arms.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start2 Mar 2020 (estimated)
- Primary completion1 Mar 2021 (estimated)
- Study completion1 Aug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mediastinal LymphadenopathyStudies 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
- Model description
- 1:1 randomisation
- Masking
- None (open label)
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Samuel V Kemp, MBBS, Principal investigator, Royal Brompton and Harefield NHS FT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04200105
- Sponsor's protocol ID
- 274281
- Status last verified
- Dec 2019
- First submitted
- 12 Dec 2019
- Last updated
- 18 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endobronchial Ultrasound Transbronchial Needle Aspiration (EBUS-TBNA) Versus the Endobronchial Ultrasound Transbronchial Needle Biopsy Using the Acquire Needle in the Assessment of Mediastinal and Hilar Lymphadenopathy: a Randomised Trial
- ClinicalTrials.gov ID
- NCT04200105
- Acronym / sponsor ID
- 274281
- Conditions
- Mediastinal Lymphadenopathy
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- Royal Brompton & Harefield NHS Foundation TrustUniversity, hospital or other
- Study start
- 2 Mar 2020 (estimated)
- Primary completion
- 1 Mar 2021 (estimated)
- Study completion
- 1 Aug 2021 (estimated)
- First posted
- 16 Dec 2019 (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.
This study aims to determine whether a new type of needle used for sampling lymph nodes (glands) around the airways of the lung, during a procedure called an endobronchial ultrasound (EBUS, provides more or better quality tissue to allow a definite diagnosis to be made than with the current standard sampling needle. Two hundred and fifty patients will be randomised to procedures using either the new or standard needle, and the results compared.
Detailed description
The causes of mediastinal lymphadenopathy include infection, reactive lymphadenopathy, granulomatous disorders, and malignancy (metastases from various primaries, lymphoma, thymoma, neurogenic tumours). Radiological appearances are usually inadequate at providing a definitive diagnosis. In granulomatous disorders such as sarcoidosis as well as certain infections including tuberculosis, there is frequently mediastinal or hilar lymph node involvement without evidence of disease activity in other organs or lymph node groups. In malignancy, the metastatic involvement of lymph nodes has important prognostic significance. However, lymph node enlargement as seen on computerised tomography (CT) scanning is a poor predictor of disease involvement, and positron emission tomography (PET) of the mediastinum has a 10-15% false positive rate. Adequate mediastinal lymph node sampling is therefore essential in order to reach a definitive diagnosis and obtain satisfactory staging information.
Mediastinal nodal sampling has traditionally been performed using invasive surgical techniques which carry significant morbidity and mortality. These procedures (cervical mediastinoscopy, anterior mediastinotomy) require general anaesthesia and a hospital inpatient stay. Some patients with significant comorbidities are therefore not considered for these procedures as they are deemed unfit for anaesthesia. Safer, less invasive, and more cost-effective procedures using endoscopic ultrasonography to guide needle aspiration of mediastinal lymph nodes have been developed. Endobronchial ultrasound (EBUS) used to guide transbronchial needle aspiration (TBNA) of mediastinal masses has, in a matter of a few years, established itself firmly within the diagnostic and staging algorithm for lung cancer, and also in the diagnosis of other causes of mediastinal and hilar lymphadenopathy such as sarcoidosis and tuberculosis. A wide range of studies has demonstrated the effectiveness and safety of this technique, with various studies reporting sensitivities of between 67% and 92%3.
EBUS-guided needle aspirates performed with 22 gauge needles yield cytological specimens which are often inadequate at providing a firm diagnosis, or at confidently excluding other malignancies such as lymphoma. Immunohistochemistry and mutational analysis are today playing a more important role in the treatment of lung cancer. There is an increasing need for larger tissue samples and ideally biopsy material to enable advanced histopathological examination of specimens. For example, a substantial percentage of lung cancers express cell surface epidermal growth factor receptors (EGFRs). Small molecules designed to inhibit the tyrosine kinase (TK) domain of the EGFR, such as gefitinib and erlotinib, have demonstrated biologic and clinical responses in patients with mutations within the EGFR-TK domain. These TK inhibitors are now an important component of the armamentarium of the thoracic oncologist in the treatment of lung cancer. It has therefore become essential to establish the EGFR mutation status of lung cancers before consideration of treatment. Mutations of the KRAS gene in lung cancer patients have been shown to confer resistance to both erlotinib and gefitinib, adding to the importance of testing tissue samples for these mutations as well. In the past, tests for EGFR and KRAS gene mutations could only be performed on block tumours post resection, however advances in molecular biology in recent years have led to the ability to test small biopsy specimens for such mutations by polymerase chain reaction (PCR) analysis, fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC). EBUS-TBNA, however, can only provide needle aspirates. These can provide samples adequate for cytological assessment, but do not always contain sufficient material to enable the formation of a cell block, thereby precluding histological assessment. Larger sized core tissue biopsy specimens are therefore likely to help in the histopathological assessment of lung cancer, and also in the diagnosis of sarcoidosis, lymphoma and other causes of mediastinal lymphadenopathy. This is likely to become even more important in the future as new clinically relevant genetic mutations are identified, and appropriate tests developed.
A novel transbronchial needle has been developed. This franseen needle has a crown tipped needle with three symmetrical cutting heels placed in a circumferential pattern designed with the intent to capture more tissue (figure 1). This needle tip was originally designed for use in interventional radiology, and is now the one of the leading designs used in endoscopic ultrasound of the gastrointestinal tract. This new needle can be passed down an EBUS scope and can hypothetically circumvent the deficiencies of EBUS-TBNA highlighted above by providing greater tissue volume for histological assessment and any subsequent molecular and genetic testing.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 1:1 randomisation
| Arm | Type | Receives |
|---|---|---|
| EBUS TBNA | Active comparator | Device: EBUS-TBNAPatients will undergo a standard EBUS examination, with sampling using a standard 22G EBUS needle. |
| Acquire TBNB | Experimental | Device: Acquire TBNBPatients will undergo a standard EBUS examination, with sampling using an Acquire TBNB needle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Scheduled for EBUS-TBNA as part of clinical care
- Lymph node size ≥5mm on CT scan
- Age > 18 years
- Written informed consent
Key exclusion criteria (2 listed)
- Contraindication to needle biopsy (e.g. coagulopathy, anticoagulation, thrombocytopenia, other bleeding diathesis)
- Inability to obtain informed consent
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 |
|---|---|---|
| EBUS-TBNAMediastinal and hilar lymph node sampling using a standard 22G EBUS needle | Device | EBUS TBNA |
| Acquire TBNBMediastinal and hilar lymph node sampling using the Acquire TBNB needle | Device | Acquire TBNB |
Primary outcome
The difference in cell volume of cancer or other diagnostic tissue obtained between the two study arms
Time frame: 1 week
7 secondary outcomes
The difference between the two study arms in the percentage of lymph nodes sampled where enough tissue is obtained for complete immunohistochemical and genetic mutation analysis.
Time frame: 1 month
The difference between the two study arms in the amount of DNA obtained.
Time frame: 1 month
The difference in complication rates between the two study arms.
Time frame: 1 month
The difference between the two study arms in yield (quantity of diagnostic material) in patients ultimately diagnosed with sarcoidosis.
Time frame: 1 month
The difference between the two study arms in yield (quantity of diagnostic material) in patients ultimately diagnosed with lymphoma.
Time frame: 1 month
The difference in sensitivity for detecting sarcoidosis between the two study arms.
Time frame: 1 month
The difference in sensitivity for detecting lymphoma between the two study arms.
Time frame: 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2019.
- Individual participant dataSharing planned: No
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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.
Samuel V Kemp, MBBS principal investigator
Royal Brompton and Harefield NHS FT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EBUS-TBNA and Acquire TBNB in people with Mediastinal Lymphadenopathy, run by Royal Brompton & Harefield NHS Foundation Trust at 1 site in United Kingdom.
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 4 inclusion and 2 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: status not confirmed, as of the sponsor's last update on 18 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Samuel V Kemp, MBBS (02073528121 ext. 88021, s.kemp@rbht.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference in cell volume of cancer or other diagnostic tissue obtained between the two study arms (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 Dec 2019.