Pulmonary NodulesSEQUENCENCT06676956
The SEQUENCE Trial
A study testing Linear EBUS first and Robotic-assisted bronchoscopy first in people with Pulmonary Nodules, run by Northwestern University at 5 sites in United States.
Trial summary
This study will randomize participants undergoing a bronchoscopic biopsy of a peripheral pulmonary nodule for their standard of care to receive robotic-assisted bronchoscopy (RaB) and then staging linear endobronchial ultrasounnd (EBUS) OR staging linear EBUS first, followed by RaB. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Pulmonary Nodules
- What is being tested?
- Linear EBUS first and Robotic-assisted bronchoscopy first
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 5 sitesUnited States
- Study dates
- 10 Nov 2024to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Peripheral Pulmonary Nodule undergoing a robotic-assisted bronchoscopy
Who cannot join
- lymph nodes that are enlarged or PET avid on CT prior to procedure
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Max Wayne
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
Jeffrey Thiboutot, jthibou1@jhmi.edu
- Recruiting
University of North Carolina, Chapel Hill
Chapel Hill, North Carolina, 27514
Jason Akulian
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Chris Kapp, MD, 312-695-3800, christopher.kapp@nm.org
- Recruiting
University of California, Davis
Sacramento, California, 95817
Jeremy Kim
About this study
Official title: The SEQUENCE Trial: Should Endobronchial Ultrasound QUeue bEfore or eNsuing to robotiC-assisted Bronchoscopy for pEripheral Pulmonary Nodule Biopsy?
This study will randomize participants undergoing a bronchoscopic biopsy of a peripheral pulmonary nodule for their standard of care to receive robotic-assisted bronchoscopy (RaB) and then staging linear endobronchial ultrasounnd (EBUS) OR staging linear EBUS first, followed by RaB. The goal of this study is to set the standard for optimizing the sequence of bronchoscopic procedures in patients at risk for early-stage malignancy.
Read the detailed description
Robotic-assisted bronchoscopy (RaB) has afforded proceduralists the ability to accurately reach the periphery of the lung for biopsy of pulmonary nodules. This has paved the way for patients to undergo both biopsy of a peripheral nodule and a staging linear endobronchial ultrasound (EBUS) in the same anesthesia event, promoting quicker throughput from discovery of a lesion to guideline-adherent treatment. Further, introduction and mainstream utilization of cone-beam CT (CBCT) has provided the bronchoscopist the ability to refine needle position with tool-in-lesion confirmation. While there are no randomized clinical trials promoting efficacy of RaB and CBCT in comparison with other bronchoscopic methods, in single center retrospective studies, diagnostic yield has consistently proven to be in the 70-85% range, superior to prior technologies.
One of the limitations of utilization of RaB and CBCT is the detrimental effect that atelectasis plays in the bronchoscopy procedure. This can lead to false positive radial EBUS (rEBUS) signals and non-diagnostic procedures. This incidence of atelectasis has been evaluated prospectively, using a protocol featuring 8-10 cmH2O of PEEP and limiting hyperoxia, and results suggest this ventilator strategy does an adequate job preventing intraprocedural lung collapse. However, this study only evaluated incidence of atelectasis and did not elaborate on its impact on diagnostic yield.
Further unknown is the optimal sequence of performance of RaB and a staging linear EBUS in patients with a radiographically normal mediastinum. Starting with either the RaB or Linear EBUS both have their pros and cons. The benefit to performance of a linear EBUS first is the potential to obviate the need for peripheral nodule biopsy by obtaining rapid, on-site pathologic feedback of occult nodal disease, reducing some of the risk of the procedure (i.e. bleeding and pneumothorax). Conversely, the pitfalls to performing linear EBUS first is the possible contribution of atelectasis resultant of the increased time from intubation to peripheral nodule biopsy, blood in the airway causing bronchospasm, and resorption atelectasis from hyperoxia. There are no prospective data evaluating this in a randomized fashion, but one Monte Carlo simulation (with assumption of diagnostic yield from navigational bronchoscopy of 70% when performed first and 60% when performed second) suggested a higher diagnostic yield and less need for repeat procedure in the navigation first group, despite a 10% assumption of occult nodal disease.
As outlined in the specific aims above, the overarching goals of this study are to assess in a multicenter, randomized clinical trial performed by members of the Interventional Pulmonary Outcomes Group (IPOG), whether sequence of staging EBUS plays a role in diagnostic yield, incidence of atelectasis, and safety outcomes in patients undergoing RaB.
- Conditions
- Pulmonary Nodules
- Being tested
- Linear EBUS first, Robotic-assisted bronchoscopy first
- Medical subject headings
- Multiple Pulmonary Nodules
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Linear EBUS firstDiagnostic test
Patients randomized to this arm will undergo a mediastinal lymph node evaluation with EBUS first, followed by biopsy followed by robotic-assisted bronchoscopy.
Robotic-assisted bronchoscopy firstDiagnostic test
Patients randomized to this arm will undergo a robotic-assisted bronchoscopy first, followed by a mediastinal lymph node evaluation with EBUS second
| Study group | Role | What they receive |
|---|---|---|
| Linear EBUS First | Active comparator | Patients will undergo a mediastinal lymph node evaluation with EBUS first, followed by biopsy followed by robotic-assisted bronchoscopy Receives: Diagnostic Test: Linear EBUS first |
| Robotic-assisted bronchoscopy first | Active comparator | Patients will undergo a robotic-assisted bronchoscopy first, followed by a mediastinal lymph node evaluation with EBUS second Receives: Diagnostic Test: Robotic-assisted bronchoscopy first |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants who received a diagnosis as a result of the procedure
This will be an outcome measure that is positive or negative based on whether a diagnosis was achieved during the procedure
Measured: This will be assessed 30 days after the procedure in a study visit that our teams conduct, it will not include the patient
Secondary outcomes (1)
Severity of atelectasis during the procedure
Using the IPOG atelectasis score (mild, moderate, and severe) we will track the impact atelectasis has on the biopsy and diagnostic yield
Measured: This will be assessed day of procedure and recorded
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2024
- Study start10 Nov 2024
- Primary completionAug 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary NodulesStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe sponsor's other registered studies.
- 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
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, University of Michigan, University of North Carolina, Chapel Hill, University of California, Davis, University of California, San Diego
- Responsible party
- Principal investigator, Christopher Kapp, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06676956
- Sponsor's protocol ID
- STU00222248 (IRB)
- Acronym
- SEQUENCE
- Status last verified
- Aug 2026
- First submitted
- 28 Oct 2024
- Last updated
- 25 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Data will be de-identified and collected in a secure REDCap database where only the lead site has access.
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The SEQUENCE Trial: Should Endobronchial Ultrasound QUeue bEfore or eNsuing to robotiC-assisted Bronchoscopy for pEripheral Pulmonary Nodule Biopsy?
- ClinicalTrials.gov ID
- NCT06676956
- Acronym / sponsor ID
- SEQUENCE / STU00222248 (IRB)
- Conditions
- Pulmonary Nodules
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Collaborators
- Johns Hopkins University, University of Michigan, University of North Carolina, Chapel Hill, University of California, Davis, University of California, San Diego
- Study start
- 10 Nov 2024 (actual)
- Primary completion
- Aug 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 6 Nov 2024 (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 will randomize participants undergoing a bronchoscopic biopsy of a peripheral pulmonary nodule for their standard of care to receive robotic-assisted bronchoscopy (RaB) and then staging linear endobronchial ultrasounnd (EBUS) OR staging linear EBUS first, followed by RaB. The goal of this study is to set the standard for optimizing the sequence of bronchoscopic procedures in patients at risk for early-stage malignancy.
Detailed description
Robotic-assisted bronchoscopy (RaB) has afforded proceduralists the ability to accurately reach the periphery of the lung for biopsy of pulmonary nodules. This has paved the way for patients to undergo both biopsy of a peripheral nodule and a staging linear endobronchial ultrasound (EBUS) in the same anesthesia event, promoting quicker throughput from discovery of a lesion to guideline-adherent treatment. Further, introduction and mainstream utilization of cone-beam CT (CBCT) has provided the bronchoscopist the ability to refine needle position with tool-in-lesion confirmation. While there are no randomized clinical trials promoting efficacy of RaB and CBCT in comparison with other bronchoscopic methods, in single center retrospective studies, diagnostic yield has consistently proven to be in the 70-85% range, superior to prior technologies.
One of the limitations of utilization of RaB and CBCT is the detrimental effect that atelectasis plays in the bronchoscopy procedure. This can lead to false positive radial EBUS (rEBUS) signals and non-diagnostic procedures. This incidence of atelectasis has been evaluated prospectively, using a protocol featuring 8-10 cmH2O of PEEP and limiting hyperoxia, and results suggest this ventilator strategy does an adequate job preventing intraprocedural lung collapse. However, this study only evaluated incidence of atelectasis and did not elaborate on its impact on diagnostic yield.
Further unknown is the optimal sequence of performance of RaB and a staging linear EBUS in patients with a radiographically normal mediastinum. Starting with either the RaB or Linear EBUS both have their pros and cons. The benefit to performance of a linear EBUS first is the potential to obviate the need for peripheral nodule biopsy by obtaining rapid, on-site pathologic feedback of occult nodal disease, reducing some of the risk of the procedure (i.e. bleeding and pneumothorax). Conversely, the pitfalls to performing linear EBUS first is the possible contribution of atelectasis resultant of the increased time from intubation to peripheral nodule biopsy, blood in the airway causing bronchospasm, and resorption atelectasis from hyperoxia. There are no prospective data evaluating this in a randomized fashion, but one Monte Carlo simulation (with assumption of diagnostic yield from navigational bronchoscopy of 70% when performed first and 60% when performed second) suggested a higher diagnostic yield and less need for repeat procedure in the navigation first group, despite a 10% assumption of occult nodal disease.
As outlined in the specific aims above, the overarching goals of this study are to assess in a multicenter, randomized clinical trial performed by members of the Interventional Pulmonary Outcomes Group (IPOG), whether sequence of staging EBUS plays a role in diagnostic yield, incidence of atelectasis, and safety outcomes in patients undergoing RaB.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linear EBUS First | Active comparator | Diagnostic Test: Linear EBUS firstPatients will undergo a mediastinal lymph node evaluation with EBUS first, followed by biopsy followed by robotic-assisted bronchoscopy |
| Robotic-assisted bronchoscopy first | Active comparator | Diagnostic Test: Robotic-assisted bronchoscopy firstPatients will undergo a robotic-assisted bronchoscopy first, followed by a mediastinal lymph node evaluation with EBUS second |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Peripheral Pulmonary Nodule undergoing a robotic-assisted bronchoscopy
Key exclusion criteria (1 listed)
- lymph nodes that are enlarged or PET avid on CT prior to procedure
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 |
|---|---|---|
| Linear EBUS firstPatients randomized to this arm will undergo a mediastinal lymph node evaluation with EBUS first, followed by biopsy followed by robotic-assisted bronchoscopy. | Diagnostic test | Linear EBUS First |
| Robotic-assisted bronchoscopy firstPatients randomized to this arm will undergo a robotic-assisted bronchoscopy first, followed by a mediastinal lymph node evaluation with EBUS second | Diagnostic test | Robotic-assisted bronchoscopy first |
Primary outcome
Number of participants who received a diagnosis as a result of the procedure
Time frame: This will be assessed 30 days after the procedure in a study visit that our teams conduct, it will not include the patient
This will be an outcome measure that is positive or negative based on whether a diagnosis was achieved during the procedure
1 secondary outcome
Severity of atelectasis during the procedure
Time frame: This will be assessed day of procedure and recorded
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2026.
- Individual participant dataSharing planned: Yes. Data will be de-identified and collected in a secure REDCap database where only the lead site has access.
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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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Linear EBUS first and Robotic-assisted bronchoscopy first in people with Pulmonary Nodules, run by Northwestern University at 5 sites in United States.
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 1 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Chris Kapp Assistant professor of medicine, MD (312-695-3800, christopher.kapp@nm.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants who received a diagnosis as a result of the procedure (time frame: This will be assessed 30 days after the procedure in a study visit that our teams conduct, it will not include the patient). 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 25 Aug 2026.