Assessing Benefits of NIRAF Detection for Identifying Parathyroid Glands During Total Thyroidectomy.

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 total thyroidectomy (TTx). It compares risk-benefits and outcomes in TTx patients where NIRAF detection with PTeye for parathyroid identification is either used or not used.

Detailed Description
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Inadvertent damage or excision of a healthy parathyroid gland (PG) following a total thyroidectomy (TTx) could result in transient hypocalcemia (< 6 months) in 5 - 35% of cases or permanent hypocalcemia (> 6 months) in 7% of the patients (1, 2). In both of these circumstances, patients would require calcium and active vitamin D supplementation in addition to a potentially prolonged hospital stay and/or unplanned hospital readmission adding to unnecessary burden and healthcare costs. These complications could be minimized with label-free intraoperative PG identification using near infrared autofluorescence (NIRAF) detection with a fiber-probe based approach (3 - 5) as utilized in 'PTeye', which is medical device that was recently FDA-cleared (6). However, the true impact of this particular NIRAF-based approach on patient outcomes is yet to be determined The aim of this prospective single blinded randomized study is to compare 2 groups of patients: TTx 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 TTx procedures with regard to postoperative hypocalcemia, PG identification, PG auto-transplantation and inadvertent resection rates compared to standard of care.

Official Title
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Assessing Benefits of Near Infrared Autofluorescence (NIRAF) Detection for Identifying Parathyroid Glands During Total Thyroidectomy.

Conditions
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Postoperative Hypoparathyroidism, Thyroid Neoplasms, Thyroid Cancer

Intervention / Treatment
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* Device: NIRAF Detection Technology


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: (i) All patients eligible for total thyroidectomy (TTx), with or without lymph node dissection. (includes patients undergoing a TTx who have undergone a prior neck exploration for parathyroid disease or other but have an intact thyroid). (ii) All patients undergoing completion thyroidectomy. Exclusion Criteria: (i) Patients with concurrent parathyroid disease. (ii) Patients with incidental enlarged parathyroid discovered during TTx. (iii) Patients undergoing thyroid lobectomy/partial thyroidectomy.

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 total thyroidectomy (TTx) with or without lymph node dissection (LND) 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 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 total thyroidectomy (TTx) with or without lymph node dissection (LND). | 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 total thyroidectomy (TTx) with or without lymph node dissection (LND). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative hypoparathyroidism/hypocalcemia (Immediate) | Postoperative low calcium (total calcium <8mg/dL or <2mmol/L) and/or undetectable parathyroid hormone (PTH) (serum intact PTH < 16 pg/mL or 1 pmol/L) within 24 hours after surgery | Within 24 hours after total thyroidectomy. | 
| Postoperative hypoparathyroidism/hypocalcemia (Transient) | Undetectable postoperative PTH and/or low calcium (total calcium < 2mmol/L or 8 mg/dL, serum intact PTH < 16 pg/mL or 1 pmol/L) at first postoperative visit (usually 5-14 days after total thyroidectomy). | 5-14 days after total thyroidectomy. | 
| Postoperative hypoparathyroidism/hypocalcemia (Permanent) | If blood calcium has not normalized at 1st postsurgical clinical visit, total calcium level is subsequently measured as necessary. Patient is defined to have permanent hypoparathyroidism if hypocalcemia persists and/or activated Vitamin D is required to be symptom free at or after the 6th postoperative month. | 6 months after total thyroidectomy | 

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 total thyroidectomy 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 total thyroidectomy 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 total thyroidectomy procedure. | 
| Number of auto-transplanted parathyroid glands | Number of auto-transplanted parathyroid glands if the parathyroid gland was accidentally excised/devascularized. | Immediate. During total thyroidectomy procedure. | 
| Number of nights spent in the hospital after total thyroidectomy | Number of nights spent for postoperative recovery in the hospital after the surgical procedure. | 0 - 72 hours after total thyroidectomy | 
| Number of inadvertently resected parathyroid glands | Number of inadvertently resected parathyroid glands when parathyroid tissue is found in the resected thyroid specimens. | Immediate (intraoperative) to 7-10 days after total thyroidectomy (as presented in the pathology report) | 
| Number of doctor visits/emergency department visits or hospital admissions | 7.8. Number of doctor visits/emergency department visits or hospital admissions due to hypocalcemia and or associated symptoms. | Up to 6 months after total thyroidectomy | 
| Duration and total daily dosage of calcium and/or vitamin D supplementation after surgery | 8.9. Duration and total daily dosage of calcium and/or vitamin D supplementation after surgery - if patient had no prior history of supplementation. | Up to 6 months after total thyroidectomy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Total Thyroidectomy, Intraoperative Parathyroid Identification, Near Infrared Autofluorescence, Postoperative Hypocalcemia, Postoperative Hypoparathyroidism