Confocal Laser Endomicroscopy VERification

NCT06079970 | Recruiting FDA Device

• 1 other identifier: NL83267.018.22
• Study Type: interventional
• Target: 208
• Locations: 7 countries
• Sites: 7

Brief Summary

The goal of this multi-center randomized clinical trial is to evaluate the added value of needle based confocal laser endomicroscopy (nCLE)-imaging to regular diagnostic bronchoscopic peripheral lung lesion analysis on the diagnostic yield in patients with peripheral pulmonary nodules suspect for malignancy. The main question\[s\] it aims to answer are: To determine if the addition of nCLE-imaging to conventional diagnostic bronchoscopic peripheral lung lesion analysis results in an improved diagnostic yield (defined as the proportion 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). Participants will undergo diagnostic bronchoscopy either with or without the addition of nCLE imaging before each TBNA. Based on the feedback of the CLE images on (in)correct placement of the needle, the needle might be repositioned before sampling. Comparison between the diagnostic yield of these groups will be done including subgroup analysis.

Conditions

Lung Cancer; Lung Neoplasm Malignant; Carcinoma, Non-Small-Cell Lung; Neoplasm of Lung

Keywords

Confocal Microscopy; Bronchoscopy; Confocal laser endomicroscopy; CLE; Fluoroscopy

Outcome Measures

Primary Outcomes (1)

• Diagnostic yield (intermediate definition)

  Diagnostic yield (defined as the proportion of patients in whom the bronchoscopic procedure results in a definitive diagnosis \[either malignant, specific benign or non-specific benign confirmed as benign in follow-up\], relative to the total number of patients that underwent the diagnostic bronchoscopic procedure). If patients with multiple lesions are included, the diagnostic yield will be computed per nodule.

  After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)

Secondary Outcomes (13)

• Diagnostic sensitivity

  After all patients have been included and followed up to 6 months after bronchoscopy (expected total time frame 2 years)

• Diagnostic yield (strict definition)

  After all patients have been included (expected total time frame 2 years)

• Procedure duration

  During procedure (bronchoscopy)

• Proportion needle repositionings and fine-tuning

  During procedure (bronchoscopy)

• Fluoroscopy time/dose

  During procedure (bronchoscopy)

Study Arms (2)

nCLE arm

EXPERIMENTAL

Diagnostic bronchoscopy is done according to institutional practice with the addition of nCLE

Device: Neelde Based Confocal Laser Endomicroscopy; Procedure: Conventional diagnostic bronchoscopy

Control arm

ACTIVE COMPARATOR

Diagnostic bronchoscopy is done according to institutional practice without the addition of nCLE

Procedure: Conventional diagnostic bronchoscopy

Interventions

Neelde Based Confocal Laser Endomicroscopy DEVICE

Confocal microscopy through the TBNA needle before tissue sampling using the Cellvizio system and AQ flex probe (Mauna Kea Technologies)

nCLE arm

Conventional diagnostic bronchoscopy PROCEDURE

Conventional diagnostic bronchoscopy with r-EBUS and optionally fluoroscopy AND/OR EMN AND/OR VB AND/OR ultrathin scope

Control arm; nCLE arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 years of age
• Suspected malignant peripheral lung lesion with an indication for a bronchoscopic diagnostic work-up as determined by the attending physician or tumor board. Peripheral pulmonary lesions are defined as lesions located beyond the visible segmental bronchi, not detectable by regular flexible bronchoscopy
• Bronchus sign on pre-procedural CT or estimated confidence for successful navigation to the nodule resulting in a r-EBUS signal
• Solid part of the lesion must be ≧10 mm
• Largest dimension of lesion size on CT ≦30 mm (long-axis)
• Ability to understand and willingness to sign a written informed consent

You may not qualify if:

• Inability or non-willingness to provide informed consent
• Endobronchial visible malignancy on bronchoscopic inspection
• Target lesion within reach of the linear EBUS scope
• Failure to comply with the study protocol
• Known allergy or risk factors for an allergic reaction to fluorescein
• Pregnancy or breastfeeding
• Hemodynamic instability
• Refractory hypoxemia
• Therapeutic anticoagulant use that cannot be withheld for an appropriate interval before the procedure
• Unable to tolerate general anesthesia according to the anesthesiologist
• Undergoing chemotherapy as several chemotherapies have fluorescent properties at the same wavelength (e.g., doxorubicin)

Sponsors & Collaborators

• Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC): lead
• Mauna Kea Technologies: collaborator

Study Sites (7)

Montefiore Medical Center

New York, New York, 10467, United States

RECRUITING

Vienna General Hospital

Vienna, Austria

NOT YET RECRUITING

General University Hospital Prague

Prague, Czechia

RECRUITING

Sotiria Hospital

Athens, Greece

RECRUITING

Morgagni Pierantoni Hospital

Forlì, Italy

NOT YET RECRUITING

Amsterdam University Medical Centers

Amsterdam, 1081 HV, Netherlands

RECRUITING

University Hospital basel

Basel, Switzerland

NOT YET RECRUITING

Related Publications (6)

• Wijmans L, Yared J, de Bruin DM, Meijer SL, Baas P, Bonta PI, Annema JT. Needle-based confocal laser endomicroscopy for real-time diagnosing and staging of lung cancer. Eur Respir J. 2019 Jun 20;53(6):1801520. doi: 10.1183/13993003.01520-2018. Print 2019 Jun.

  PMID: 31023849 BACKGROUND

• Kramer T, Wijmans L, van Heumen S, Bansal S, Jeannerat D, Manley C, de Bruin M, Bonta PI, Annema JT. Needle-based confocal laser endomicroscopy for real-time granuloma detection. Respirology. 2023 Oct;28(10):934-941. doi: 10.1111/resp.14542. Epub 2023 Aug 10.

  PMID: 37562791 BACKGROUND

• Manley CJ, Kramer T, Kumar R, Gong Y, Ehya H, Ross E, Bonta PI, Annema JT. Robotic bronchoscopic needle-based confocal laser endomicroscopy to diagnose peripheral lung nodules. Respirology. 2023 May;28(5):475-483. doi: 10.1111/resp.14438. Epub 2022 Dec 19.

  PMID: 36535801 BACKGROUND

• Kramer T, Wijmans L, de Bruin M, van Leeuwen T, Radonic T, Bonta P, Annema JT. Bronchoscopic needle-based confocal laser endomicroscopy (nCLE) as a real-time detection tool for peripheral lung cancer. Thorax. 2022 Apr;77(4):370-377. doi: 10.1136/thoraxjnl-2021-216885. Epub 2021 Jun 25.

  PMID: 34172559 BACKGROUND

• Vachani A, Maldonado F, Laxmanan B, Kalsekar I, Murgu S. The Impact of Alternative Approaches to Diagnostic Yield Calculation in Studies of Bronchoscopy. Chest. 2022 May;161(5):1426-1428. doi: 10.1016/j.chest.2021.08.074. Epub 2021 Sep 7. No abstract available.

  PMID: 34506792 BACKGROUND

• van Heumen S, Kramer T, Korevaar DA, Gompelmann D, Bal C, Hetzel J, Jahn K, Poletti V, Ravaglia C, Sadoughi A, Stratakos G, Bakiri K, Koukaki E, Anagnostopoulos N, Votruba J, Sestakova Z, Heuvelmans MA, Daniels JMA, de Bruin DM, Bonta PI, Annema JT. Bronchoscopy with and without needle-based confocal laser endomicroscopy for peripheral lung nodule diagnosis: protocol for a multicentre randomised controlled trial (CLEVER trial). BMJ Open. 2024 Jul 4;14(7):e081148. doi: 10.1136/bmjopen-2023-081148.

  PMID: 38964802 DERIVED

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Jouke Annema, Prof. dr.

  Amsterdam UMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Saskia van Heumen, MSc

CONTACT

+31(0)20 566 2694; s.vanheumen@amsterdamumc.nl

Jouke Annema, Prof. dr.

CONTACT

j.t.annema@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr. J.T. Annema

Study Record Dates

• First Submitted: October 2, 2023
• First Posted: October 12, 2023
• Study Start: October 18, 2023
• Primary Completion: October 18, 2025
• Study Completion: October 18, 2025
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Access Criteria: Upon reasonable request

Locations

US (1); CZ (1); AU (1); NL (1); IT (1); GR (1); CH (1)