Evaluating Impact of NIRAF Detection for Identifying Parathyroid Glands During Parathyroidectomy

Study Overview
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Brief Summary
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This study describes a single center, randomized, single-blinded clinical trial to assess the clinical benefits of the use of near infrared autofluorescence (NIRAF) detection with an FDA-cleared device 'Parathyroid Eye (PTeye)' for identifying parathyroid glands (PGs) during parathyroidectomy (PTx) procedures. It compares risk-benefits and outcomes in PTx patients where NIRAF detection with PTeye for parathyroid identification is either used or not used.

Detailed Description
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Inability of the surgeon to identify or localize the diseased PG can occur in 5 - 10% of cases resulting in failed parathyroidectomies (PTx). As a result, persistent hyperparathyroidism can occur in these patients resulting in unnecessary repeat surgeries that may be associated with increased morbidity and costs. Ultrasound imaging, 99mTechnetium-sestamibi scintigraphy, and computed tomography (CT) have so far demonstrated variable efficacy in preoperative localization of diseased PGs and may not always correlate well with the surgical field of view as observed intraoperatively. Consequently, most surgeons rely on visual identification of PGs during surgery, whereby the accuracy of PG identification is eventually determined by her/his surgical skill and experience. When in doubt, a surgeon routinely confirms the identity of PG tissue intraoperatively by sending the specimen for frozen section analysis that typically requires a wait time of 20-30 minutes per sample and has additional costs. By easily being able to distinguish parathyroid from other tissues intraoperatively, postsurgical complications and associated costs may be reduced. The unique discovery of near infrared autofluorescence (NIRAF) in parathyroid tissues demonstrated that optical modalities that detect NIRAF can be utilized for non-invasive and label-free identification of parathyroid tissues with an accuracy as high as 97%. Since then, several research groups have explored the feasibility of localizing parathyroid glands using NIRAF detection with reasonable success, resulting in FDA clearance for marketing this optical technique. In this study, we plan to evaluate whether an FDA-cleared device called 'PTeye' (AiBiomed, Santa Barbara, CA) is beneficial or not, for the surgeon and patient during PTx operations. The results of such a study will help us to understand and assess the true impact of optical modalities such as PTeye on (i) improving the quality and efficiency of PTx surgeries and (ii) minimizing risk of postsurgical complications and related expenses. The aim of this prospective single blinded randomized study is to compare 2 groups of patients: PTx patients operated using NIRAF detection technology with PTeye as adjunct tool (NIRAF+) vs. patients operated without the adjunct technology (NIRAF-). The main objective of this study is to assess the benefit of intraoperative use of NIRAF detection technology via PTeye during PTx procedures with regard to PG identification, duration of surgery, number of frozen section analysis performed, number of intraoperative PTH assays sent and incidence of postsurgical complications, if any and history of ER visits or hospitalization or repeat surgeries due to persistent high blood calcium after PTx procedure, compared to standard of care.

Official Title
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Evaluating Impact of Near Infrared Autofluorescence (NIRAF) Detection for Identifying Parathyroid Glands During Parathyroidectomy

Conditions
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Parathyroid Adenoma, Parathyroid Neoplasms, Parathyroid Hyperplasia, Parathyroid Cancer, Hypercalcemia, Primary Hyperparathyroidism

Intervention / Treatment
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* Device: NIRAF Detection Technology


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All primary hyperparathyroidism patients eligible for parathyroidectomy (PTx). Both bilateral and focused mode of PTx will be considered for this study, based on the surgeon's preference. Re-operative primary hyperparathyroidism patients who have undergone a failed prior PTx. Exclusion Criteria: Patients with concurrent parathyroid and thyroid disease that require total thyroidectomy. Patients with secondary or tertiary hyperparathyroidism.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: NIRAF detection technology is used as an adjunctive tool for intraoperative parathyroid identification in patients who undergo parathyroidectomy (PTx) in the interventional group. Generic Name of Device: Parathyroid Autofluorescence Detection Device (NIRAF detection technology). The Parathyroid Autofluorescence Detection Device consists of a disposable fiber-optic probe that emits non-ionizing radiation from a near infrared (NIR) 785 nanometer (nm) laser source, and also transmits the resulting tissue NIRAF to a photo-detector. The 785 nm laser source emits a maximum power of 20 milliwatts (mW). The device has an FDA clearance for clinical use in general surgeries and dermatological use (Class 2 device).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NIRAF Detection Technology +<br>Parathyroid gland identification will be performed with PTeye using NIRAF detection technology as an adjunctive tool in patients who undergo parathyroidectomy (PTx). | Device: NIRAF Detection Technology<br>* Near Infrared Autofluorescence (NIRAF) detection technology or 'PTeye' consists of a disposable fiber-optic probe that emits non-ionizing radiation from a NIR 785 nm laser source, and also transmits the resulting tissue NIRAF to a photo detector. The 785 nm laser source emits a maximum power of 20 mW. The device is FDA cleared for clinical use in general surgeries and dermatological use (Class 2 device). After surgeon identifies a potential parathyroid gland in the surgical field, the surgeon places the fiber-optic probe of PTeye on suspect tissue and presses the device foot-pedal to activate tissue NIRAF measurement. Auditory beep at high frequency with a Detection Ratio > 1.2 is interpreted by device as the suspect tissue being positive for parathyroid.<br>* Other names: PTeye Device;|
| No Intervention: NIRAF Detection Technology -<br>Parathyroid gland identification will be performed with the naked eye of the surgeon without using PTeye - NIRAF detection technology in patients who undergo parathyroidectomy (PTx). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent hyperparathyroidism (Immediate) | Failure of intra-operative parathyroid hormone (PTH) to normalize (defined as failure of PTH to drop > 50% of its baseline value at final intra-operative PTH assay and/or failure of PTH to drop < 65 pg/ml or 6.9 pmol/L). | During parathyroidectomy (PTx) procedure | 
| Persistent hyperparathyroidism or hypercalcemia (transient) | Elevated blood calcium levels (total blood calcium level > 10.5 mg/dL or 2.6 mmol/L) with/without elevated parathyroid hormone (PTH) (serum intact PTH > 65 pg/ml or 6.9 pmol/L) at first postoperative visit. | 5-14 days after PTx procedure | 
| Persistent hyperparathyroidism or hypercalcemia (failed parathyroidectomy) | If blood calcium with/without parathyroid hormone (PTH) has not normalized at 1st post-operative visit, calcium and/or PTH is subsequently measured as necessary. Patient is defined to have a failed parathyroidectomy if hypercalcemia/hyperparathyroidism (defined as total blood calcium level > 10.5 mg/dL or 2.6 mmol/L, with/without elevated serum intact PTH > 65 pg/ml or 6.9 pmol/L) persists at or after the 6th postoperative month. | 6 months after PTx procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall number of parathyroid glands identified | Overall number of parathyroid glands identified (Experimental Group: Glands identified with naked eye + NIRAF; Control Group: Glands identified with naked eye) | Immediate. During PTx procedure. | 
| Number of parathyroid glands identified with NIRAF | Number of parathyroid glands identified with NIRAF, which was not seen with surgeon's naked eye | Immediate. During PTx procedure. | 
| Number of frozen sections sent for analysis | Number of frozen sections sent for analysis during the procedure to confirm potential parathyroid tissue | Immediate. During PTx procedure. | 
| Number of diseased parathyroid glands identified versus preoperatively localized glands | Number of diseased parathyroid glands identified intra-operatively versus glands localized preoperatively using sestamibi, CT or ultrasound | Preoperative to immediate during PTx procedure. | 
| Number of intra-operative parathyroid hormone (PTH) assays sent | Number of intra-operative parathyroid hormone assays sent during the procedure | Immediate. During PTx procedure. | 
| Duration taken to identify first parathyroid gland | Duration taken to identify 1st parathyroid gland in PTx procedure - timed from skin incision to finding PG. | Immediate. During PTx procedure. | 
| Duration taken to identify last parathyroid gland | Duration taken to identify last parathyroid gland in PTx procedure - timed from skin incision to finding the last PG. | Immediate. During PTx procedure. | 
| Duration of parathyroidectomy (PTx) procedure | Duration of PTx procedure - timed from skin incision until the surgeon notifies the anesthesia team to awaken the patient | Immediate. During PTx procedure. | 
| Duration taken for intraoperative parathyroid hormone (PTH) to normalize | Time taken for PTH to attain cure criteria or normalize - timed from skin incision until the PTH levels drops > 50% of its baseline value and/or PTH drops < 65 pg/ml or 6.9 pmol/L. | Immediate. During PTx procedure. | 
| Number of nights spent in the hospital after parathyroidectomy | Number of nights spent for postoperative recovery in the hospital after the surgical procedure. | 0-72 hours after PTx procedure. | 
| Number of 'false positive' tissues excised by surgeon | Number of tissues that were excised by surgeon assumed to be parathyroid tissue, but is later validated as non-parathyroid tissue (false positive) by histology | Immediate to 10 days after PTx procedure. | 
| Number of doctor visits/emergency department visits or hospital admissions | Number of doctor visits/emergency department visits or hospital admissions due to persistent hypercalcemia and/or associated symptoms after parathyroidectomy procedure | Up to 6 months after PTx procedure. | 
| Number of patients who have had repeat parathyroidectomy (PTx) procedure | Number of patients with repeat PTx procedure performed after the current procedure | 6 - 12 months after PTx procedure. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parathyroidectomy, Intraoperative Parathyroid Identification, Near Infrared Autofluorescence, Persistent Hyperparathyroidism, Persistent Hypercalcemia, Failed Parathyroidectomy, Repeat Parathyroidectomy