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| ID | Type | Description | Link |
|---|---|---|---|
| Republic of Korea | Other Identifier | VPIX Medical Inc. |
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Delays in specimen recruitment have increased costs and strained resources, risking study validity. To maintain ethical and scientific integrity, the study will be terminated early.
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| Name | Class |
|---|---|
| Unity Health Toronto | OTHER |
| Korea University Anam Hospital | OTHER |
| Samsung Medical Center | OTHER |
| Seoul National University Hospital |
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Intra-operative evaluation of residual brain tumor currently relies on frozen-section histopathology, which typically requires 20-30 minutes for tissue processing and interpretation, prolonging operative time and increasing staffing demands. Confocal Laser Fluorescence Microscopy (cCeLL - Ex vivo) acquires real-time, high-resolution fluorescence images of resected tissue and therefore may serve as a rapid alternative or adjunct to frozen sections. This prospective, multi-center study was designed to systematically assess the clinical performance of cCeLL - Ex vivo during brain-tumor surgery.
Primary Objective
Demonstrate non-inferiority of cCeLL - Ex vivo versus frozen-section histopathology in terms of clinical sensitivity and specificity for intra-operative brain-tumor diagnosis.
Secondary Objectives Compare diagnostic turnaround time between cCeLL - Ex vivo and frozen section. Evaluate tumor-type classification accuracy for each modality. Determine the average number of images required for definitive cCeLL - Ex vivo interpretation.
Quantify overall diagnostic performance of cCeLL - Ex vivo using the area under the ROC curve (AUC).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients already scheduled for brain tumor surgery | Experimental | Study Arms and Intervention This study compares cCeLL - Ex vivo imaging (test) and frozen section histopathology (control) against permanent section histopathology (reference standard).
The study evaluates diagnostic accuracy, sensitivity, and specificity of cCeLL - Ex vivo imaging. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| cCeLL - Ex vivo | Diagnostic Test | Neoplastic brain tissue biopsied from participant will be visualized, and images will be captured using cCeLL - Ex vivo. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Sensitivity for Tumor Detection (Specimen-level) | The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 283 tumor specimens are presented below. | From neurosurgical resection to permanent pathology (≈ 4 weeks) |
| Clinical Specificity for Tumor Detection (Specimen-level) | The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 39 normal specimens are as follows | From neurosurgical resection to permanent pathology (≈ 4 weeks) |
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Inclusion Criteria
Specimens and images used in this study must meet all of the following criteria:
Exclusion Criteria
Specimens and images that meet any of the following criteria will be excluded from the study:
Emergency cases where informed consent could not be obtained before surgery.
Specimens with significant hemorrhage, affecting image quality.
Small biopsy specimens that do not meet the required size for imaging.
Poor-quality images that do not meet study criteria, including:
Cases deemed inappropriate for the study by the principal investigator or study staff due to ethical concerns or potential impact on study results.
Patients undergoing multiple surgeries at the same site.
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| Name | Affiliation | Role |
|---|---|---|
| Sunit Das, MD,MMSc,PhD | Unity Health- St. Michael's Hospital | Principal Investigator |
| Shin-Hyuk Kang, MD,MMSc,PhD | Korea University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Michael's Hospital | Toronto | Ontario | M5B 1W8 | Canada | ||
| Korea University Anam Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14519550 | Background | Amos WB, White JG. How the confocal laser scanning microscope entered biological research. Biol Cell. 2003 Sep;95(6):335-42. doi: 10.1016/s0248-4900(03)00078-9. | |
| Background | BIS Research Inc. Medical market data. Updated 2022. https://blog.bisresearch.com/bis-research-market-insights-quick-bytes | ||
| Background | Carl Zeiss Meditec AG. Convivo: Putting in vivo cellular imaging at your fingertips. 2019:Brochure. Available at: https://www.zeiss.com/content/dam/Meditec/ref_master/products/convivo/documents/convivo_brochure.pdf | ||
| 27279685 |
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This was a single-group, assessor-blinded study with no randomization or run-in period. Adults (≥19) with suspected brain tumors who consented were enrolled. A total of 285 Patient at four sites (three in Korea, one in Canada) joined; Each could yield up to three specimens, resulting in 322 analyzable samples. No comparator was used, so all proceeded to cCeLL - Ex vivo. No extra screening or washout was performed.
Recruitment Status: Completed / Enrolled: 285 patients, 358 specimens, drop-out 36 speciments Study Start: Jan 1, 2023 , Primary y Completion: Nov 27, 2024 First enrollment: Korea: Jan 1, 2023 Canada: Jul 5, 2024 Enrollment ended: Korea: Nov 27, 2024 / Canada: Oct 18, 2024 Analyzed: 322 specimens Study Completion Date (database lock and QC): 31 Dec 2024
| ID | Title | Description |
|---|---|---|
| FG000 | Participants | "All participants underwent the same imaging intervention (cCeLL - Ex vivo); Participant Flow counts are reported for both participants and the tissue-specimen units analyzed." |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
The final analyzable dataset consisted of 271 participants(322 specimens)
| ID | Title | Description |
|---|---|---|
| BG000 | CeLL - Ex Vivo Imaging | All resected brain-tumor specimens were imaged in the operating room with cCeLL - Ex vivo, a confocal laser fluorescence endomicroscope that captures real-time, sub-cellular resolution images. Blinded expert pathologists interpreted the images on a secure workstation. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age in years at the time of neurosurgical resection, calculated from date of birth. Reported as mean ± SD |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Clinical Sensitivity for Tumor Detection (Specimen-level) | The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 283 tumor specimens are presented below. | Both tumor and non-tumor specimens were collected from 19 participants. | Posted | Number | 95% Confidence Interval | Percentage of tumor specimens (%) | From neurosurgical resection to permanent pathology (≈ 4 weeks) | specimens | specimens |
|
|
From specimen collection during surgery through final pathology reporting (up to 4 weeks post-surgery)
Adverse events were actively monitored for all 285 participants from specimen collection through final pathology reporting; no adverse events were observed.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Single Group: cCeLL - Ex vivo and Frozen Section | All enrolled participants underwent neurosurgical resection for suspected brain tumors. Resected specimens were examined using the investigational device, cCeLL - Ex vivo (confocal fluorescence endomicroscopy), as well as the standard frozen section procedure. Permanent section served as the final reference standard for comparison. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Min-Jae Jeong | VPIX Medical, Inc | 82425350676 | clinical@vpixmedical.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 6, 2024 | Aug 12, 2025 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Mar 3, 2023 | Apr 8, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| OTHER |
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This trial employed an assessor-blinded design. Specifically, the pathologist who interpreted the cCeLL - Ex vivo images had no access to the patient's clinical information, frozen section results, or permanent section results. By ensuring that the individual responsible for cCeLL - Ex vivo image interpretation was blinded to other diagnostic data, the study minimized bias in determining sensitivity and specificity outcomes.
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| Seoul |
| South Korea |
| Samsung Medical Center | Seoul | South Korea |
| Seoul National University Hospital | Seoul | South Korea |
| Background |
| Chand P, Amit S, Gupta R, Agarwal A. Errors, limitations, and pitfalls in the diagnosis of central and peripheral nervous system lesions in intraoperative cytology and frozen sections. J Cytol. 2016 Apr-Jun;33(2):93-7. doi: 10.4103/0970-9371.182530. |
| 31862245 | Background | de Martel C, Georges D, Bray F, Ferlay J, Clifford GM. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob Health. 2020 Feb;8(2):e180-e190. doi: 10.1016/S2214-109X(19)30488-7. Epub 2019 Dec 17. |
| Background | Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer; 2020 (https://gco.iarc.fr/today, accessed February 2021). |
| Background | IndustryARC. Oncology Market - Forecast (2020 - 2025). 2020. |
| 30803189 | Background | Mat Zin AA, Zulkarnain S. Diagnostic Accuracy of Cytology Smear and Frozen Section in Glioma. Asian Pac J Cancer Prev. 2019 Feb 26;20(2):321-325. doi: 10.31557/APJCP.2019.20.2.321. |
| Background | Mauna Kea Technologies. Cellvizio: Real-time in vivo cellular imaging platform. 2021:Brochure. Available at: http://www.cellvizio.net/uploads/media/media_pdf/0001/03/MKT-132-EN-Cellvizio%20Web%20Brochure.pdf |
| Background | MAVIG GmbH. Vivascope: Confocal laser scanning microscopy - In vivo histology for cellular level skin analyses in cosmetic research and dermopharmacy. 2019:Brochure. Available at: https://www.vivascope.de/wp-content/uploads/2019/06/Cosmeticbrochure.pdf |
| Background | Samal S, Kalra R, Sharma J, et al. Comparison between crush/squash cytology and frozen section preparation in intraoperative diagnosis of central nervous system lesions. Oncol J India. 2018;1:25-30. |
| 25593754 | Background | Tofte K, Berger C, Torp SH, Solheim O. The diagnostic properties of frozen sections in suspected intracranial tumors: A study of 578 consecutive cases. Surg Neurol Int. 2014 Dec 3;5:170. doi: 10.4103/2152-7806.146153. eCollection 2014. |
| 3112165 | Background | White JG, Amos WB, Fordham M. An evaluation of confocal versus conventional imaging of biological structures by fluorescence light microscopy. J Cell Biol. 1987 Jul;105(1):41-8. doi: 10.1083/jcb.105.1.41. |
| Background | WHO. Assessing national capacity for the prevention and control of noncommunicable diseases: report of the 2019 global survey. Geneva: World Health Organization; 2020. |
| Specimens |
|
| Mean |
| Standard Deviation |
| years |
| Participants |
|
|
| Sex: Female, Male | Sex assigned at birth, obtained from medical records. Reported as count and percentage of participants | Count of Participants | Participants | Participants |
|
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants | Participants |
|
| Baseline Number of Tissue Specimens Collected for cCeLL - Ex vivo Imaging | Number | Specimens | Participants |
|
|
| Participants |
|
| specimens |
|
|
|
| Primary | Clinical Specificity for Tumor Detection (Specimen-level) | The diagnostic results of cCeLL - Ex vivo imaging interpretation by experts and frozen section examination for 39 normal specimens are as follows | Both tumor and non-tumor specimens were collected from 19 participants. | Posted | Number | 95% Confidence Interval | Percentage of normal specimens (%) | From neurosurgical resection to permanent pathology (≈ 4 weeks) | specimens | specimens |
|
|
|
|
| 0 |
| 285 |
| 0 |
| 285 |
| 0 |
| 285 |
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| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| Non-Inferiority |
The non-inferiority margin was set at 0.10 for specificity |
f any secondary analyses could not fit into the above format (e.g., AUC analysis, time efficiency), they were reported as descriptive statistics rather than hypothesis testing |