nCLE-Cone-beam CT Navigation Bronchoscopy

Combined Needle-based Confocal Laser Endomicroscopy Cone-Beam Computed Tomography Navigation Bronchoscopy: a Proof of Principle Study

The goal of this proof of principle observational study is to investigate in patients with suspected peripheral pulmonary nodules. The main question it aims to answer is:

• What is the concordance between CBCT navigation success (tool-in-lesion on CBCT spin) and nCLE tool-in-lesion confirmation (tool-in-lesion nCLE criteria observed).

Participants scheduled to undergo a diagnostic conebeam navigation bronchoscopy will be included in the study. nCLE imaging at the tip of the TBNA needle will be added to the procedure for study purposes.

Two needle punctures of the pulmonary nodule will be followed by nCLE imaging directly followed by a tool-in-lesion CBCT spin in order to compare nCLE results with CBCT results.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer; Lung Neoplasm; Peripheral Lung Parenchyma Tumor
• Intervention / Treatment: Device: needle-based confocal laser endomicroscopy

Detailed Description

Lung cancer remains a significant problem in current society with one of the higher cancer related mortality rates. The increased use of chest computed tomography (CT) and the po-tential future lung cancer screening result in an increased detection of early-stage peripheral lung cancer. Bronchoscopies are often indicated to collect tissue for diagnosis and to aid treatment decision making.

Diagnostic bronchoscopy for peripheral lung nodules remains challenging despite many tech-nological innovations. The procedure comprises three essential pillars needed for a diagnos-tic success: navigation to the lesion, tool-in-lesion confirmation and adequate tissue retrieval.

Cone beam computed tomography navigation bronchoscopy (CBCT-NB) is a fairly new tech-nique that provides coarse navigation to the pulmonary lesion with real-time guidance using augmented fluoroscopy (AF). An initial CBCT scan allows for segmentation of the target le-sion and selecting the optimal pathway. Repeated CBCT scanning allows for confirmation that the target has been reached (navigation success) or if repositioning is needed.

Although the technique is very promising, an often discussed disadvantage of CBCT is the inherent use of ionizing radiation, limited availability and challenges with small nodules lo-cated in the basal and posterior fields due to respiratory motion. Most procedures ask for multiple CBCT spins both for trajectory planning, tool adjustments and tool-in-lesion confir-mation. This, combined with extensive use of fluoroscopy is associated with radiation expo-sure for both patients and the investigation team. Additionally, CBCT-NB with AF provides information from a global perspective rather than a local perspective. In experienced centers, coarse navigation guidance seems of lesser concern and fine positioning and optimal tissue sampling are the biggest problems to be overcome. The persistently low diagnostic yield of navigation bronchoscopies can for the majority be attributed mispositioning of the tools in "the last centimeter". Therefore there is a need for complementary techniques providing real-time information for fine-tuning the needle position such as needle-based confocal laser en-domicroscopy (nCLE) also called the "smart needle".

Confocal laser endomicroscopy (CLE) is a high-resolution microscopic technique that visual-izes individual cells in real-time at the tip of the biopsy needle, allowing for real-time micro-scopic feedback for fine tuning needle positioning and tool-in-lesion confirmation. Currently, it is unknown which (combination of) techniques are the most optimal (i.e., leading to a high di-agnostic yield and cost-effective). Therefore, research is needed to investigate the potential of new (combinations of) techniques. To date, there are no reports on the combination of CBCT-NB with nCLE.

Objective: This study aims to investigate proof of principle of utilizing nCLE during CBCT-NB navigation bronchoscopy. A confirmatory CBCT spin is considered the gold standard for tool-in-lesion but is associated with additional radiation exposure. The aim is to investigate the concordance between CBCT navigation success (tool-in-lesion on CBCT spin) and nCLE tool-in-lesion confirmation (tool-in-lesion nCLE criteria observed). The investigators also hypothesize that nCLE could reduce or replace the need for additional confirmatory CBCT scans and limit fluoroscopy use.

Study design: Investigator-initiated proof of principle medical device study

Study population: Patients (18 years and older) with (suspected) pulmonary nodules with an indication for cone-beam computed tomography navigation bronchoscopy.

Procedure: Cone beam computed tomography navigation bronchoscopy combined with needle-based confocal laser endomicroscopy.

Main study parameters/endpoints:

• CBCT-NB navigation success as either tool-in-lesion OR unsuccessful
• nCLE tool-in-lesion confirmation, defined as tool-in-lesion nCLE criteria observed

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Amsterdam UMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Study Population

Patients with a suspected malignant peripheral pulmonary nodule(s) referred for CBCT-NB for tissue sampling.

Description

Inclusion Criteria:

• 18 years or older
• Suspected pulmonary nodule with an indication for CBCT-NB (decided by multidisciplinary tumour board)
• Nodule must be solid or partially solid
• Solid part of the nodule must be at least 8 mm
• Largest dimension of the nodule on CT equal or less than 30 mm
• Ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

• Inability or non-willingness to provide informed consent
• Patients with an endobronchial visible lung tumor on bronchoscopic inspection
• Patients in which the target lesion is within reach of the linear EBUS scope
• Lung nodules that resolved at the time of index intraprocedural CBCT
• Failure to comply with the study protocol
• Patients with known allergy for fluorescein or risk factors for an allergic reaction
• Pregnant or breastfeeding women
• Patients with hemodynamic instability
• Patients with refractory hypoxemia
• Patients with a therapeutic anticoagulant that cannot be held for an appropriate in-terval before the procedure
• Patients who are unable to tolerate general anesthesia according to the anesthesiologist
• Patient undergoing chemotherapy as several chemotherapies have fluorescent properties at the same wavelength (e.g. doxorubicin)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: nCLE + CBCT-NB; Patients with a suspected malignant peripheral pulmonary nodule(s) referred for cone beam ct navigation bronchoscopy for tissue sampling.	Device: needle-based confocal laser endomicroscopy; needle-based confocal laser endomicroscopy at the tip of the TBNA needle for two punctures, combined with confirmatory CBCT spin for tool-in-lesion confirmation; Other Names: cone beam computed tomography navigation bronchoscopy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CBCT navigation success and nCLE tool-in-lesion confirmation	CBCT-NB navigation success: tool-in-lesion OR unsuccessful navigation nCLE tool-in-lesion confirmation: in-lesion nCLE criteria seen	Intra-procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical feasibility	Proportion of nCLE imaging that are successful (meaning that the preloaded needle can be advanced through the working channel, puncture the nodule, advance the CLE probe and start imaging) resulting good quality images.	Intra-procedure
Safety	Number and proportion of (severe) adverse events ((S)AEs) and investigational procedure related adverse events (AEs)	Up to 7 days post procedure
Diagnostic yield	Proportion (expressed in percentages) of patients in whom the bronchoscopic procedure results in a definitive diagnosis out of the total number of patients that have received the diagnostic bronchoscopic procedure.	up to 6 months post procedure
Diagnostic sensitivity for malignancy	Proportion (expressed in percentages) of patients that have malignancy diagnosed by bronchoscopic tissue sampling, relative to the total number of patients with a final diagnosis of malignancy as determined by the reference standard.	up to 6 months post procedure
Sensitivity, specificity and accuracy of real-time nCLE imaging assessment	Sensitivity, specificity and accuracy of real-time nCLE imaging assessment all described in percentages.	Intra-procedure
Sensitivity, specificity and accuracy of post-procedure nCLE image assessment	Sensitivity, specificity and accuracy of post-procedure nCLE image assessment described as percentages.	Intra-procedure
Interobserver agreement (IOA) and intraobserver reliability (IOR)	Interobserver agreement (IOA) represented by the Cohen's kappa statistics (mean with 95% confidence intervall) and intraobserver reliability (IOR) represented by the Cohen's kappa statistics (mean +/- standard deviation)	Intra-procedure

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total procedure duration	Total procedure duration in minutes (introduction brochoscope to removal of bronchoscope)	Intra-procedure

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Jouke Annema, MD, PhD, Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2024
• Primary Completion (Actual): December 16, 2025
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: July 11, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Bronchoscopy; Cone beam computed tomography; Confocal Laser Endomicroscopy; Image guided bronchoscopy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms
• Other Study ID Numbers: NL86502.018.24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No