Comparison of Fluorescein-INtra-VItal Microscopy Versus Conventional Frozen Section Diagnosis for intraOperative Histopathological Evaluation

NCT ID: NCT04597801

Last Updated: 2022-11-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 210 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-30
• Study Completion Date: 2022-08-03

Brief Summary

With the appliance of the in-vivo microscopy after Fluorescein staining, the investigators hypothesize that the preliminary in-vivo histopathological diagnostic accuracy is not inferior to conventional frozen section analysis accuracy when using the final histopathological result as gold standard.

Detailed Description

In neurosurgery, intraoperative histopathological frozen section analysis (cryosection) offers a crucial tool for the rapid assessment of tumor entity and dignity and the creation of tumor-free resection margins. The method, however, remains unreliable and time-consuming, sometimes prolonging surgical times and demonstrating diagnostic accuracy for frozen section in glioma ranging from 78.4% to 95% in comparison to the final histopathology, depending on the technique used.2,3 To combat these shortcomings, another promising adjunct was developed in the form of intraoperative dye-dependent in-vivo microscopy, for which there has been little scientific evidence so far, with only a few recent studies exploring its utility, safety and general applicability. The theoretical idea of the technique in principle is to allow for histopathological assessment of tumor tissue in-vivo without the need for time-consuming fixation and transport of resected tissue biopsies, aiming for a so-called in-situ digital biopsy and thereby substantially improving operative precision and surgical times. It stands to reason that the benefit in visualization provided by fluorescein staining may further be driven through in-vivo microscopy. Altogether, with the use of fluorescein sodium in in-vivo microscopy, the operating surgeon may in the future inspect supposedly malignant fluorescent tissue first-hand, evaluate it for tumorous cells in real-time and adjust their resection strategy in a far more immediate fashion.

Conditions

Intracranial Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Fluorescein sodium

A single dose of fluorescein sodium is applied before brain tumor resection. 20-40 minutes prior to the planned tumor resection, a bolus of 5 mg per kg body weight is administered intravenously, staining tumor tissue with fluorescent dye to visualize tumor cells.

Group Type: EXPERIMENTAL

Alcon

Intervention Type: DRUG

Fluorescein sodium is administered intravenously with a bolus injection of 5 mg per kg of bodyweight 20-40 minutes prior to the planned tumor resection.

Interventions

Alcon

Fluorescein sodium is administered intravenously with a bolus injection of 5 mg per kg of bodyweight 20-40 minutes prior to the planned tumor resection.

Intervention Type: DRUG

Other Intervention Names

Fluorescein sodium

Eligibility Criteria

Inclusion Criteria

1. Age ≥18 years

2. Signed informed consent

3. Suspected intracranial tumor revealed by cranial magnetic resonance imaging (according to clinical routine) scheduled for resection with intraoperative frozen section evaluation

Exclusion Criteria

1. Known allergic or suspected allergic reactions to fluorescein sodium

2. Liver disease, CHILD B or C

3. Patients under medication with beta-blockers, digoxin, chinidin and probenecid as well as inhibitors of glucuronidation, such as immunosuppressants, when the medication must not be discontinued perioperatively

4. Patients with relevant congenital limitations of glucuronidation performance (e.g. Rotor syndrome, Gilbert-Meulengracht syndrome, Crigler-Najjar syndrome)

5. Patients with terminal renal failure requiring hemodialysis

6. Inability to provide informed consent

7. Pregnancy (incl. positive pregnancy test)

8. Women of childbearing age must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate (i.e. less than 1% per year) when used consistently and correct are such as implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Carl Zeiss Meditec AG

INDUSTRY

Sponsor Role: collaborator

Technical University of Munich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jens PD Gempt, MD

Role: STUDY_CHAIR

Technische Universität München, Klinik und Poliklinik für Neurochirurgie

Locations

Universitätsklinikum Mannheim

Mannheim, , Germany

Technische Universität München, Klinik und Poliklinik für Neurochirurgie

München, , Germany

Universitätsklinikum Regensburg

Regensburg, , Germany

Countries

Germany

Other Identifiers

INV-GEM-0200-I

Identifier Type: -

Identifier Source: org_study_id