Evaluating Impact of NIRAF Detection for Identifying Parathyroid Glands During Parathyroidectomy (NIRAF)

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Hyperparathyroidism; Parathyroid Neoplasms; Hypercalcemia; Parathyroid Adenoma; Parathyroid Cancer; Parathyroid Hyperplasia
• Intervention / Treatment: Device: NIRAF Detection Technology

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NIRAF Detection Technology +; 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; 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.; Other Names: PTeye Device
No Intervention: NIRAF Detection Technology -; 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?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Number of Parathyroid Glands Identified With High Confidence Per Patient	Average number of parathyroid glands identified (Experimental Group: Glands identified with naked eye + NIRAF; Control Group: Glands identified with naked eye) per patient	Immediate. During PTx procedure.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 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
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.
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.
Number of Participants Stratified by Duration of Hospital Stay	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 Patients Who Have Had Repeat Parathyroidectomy (PTx) Procedure	Number of patients with repeat PTx procedure performed after the current procedure.	At 6-months post-operation

Collaborators and Investigators

• Sponsor: Vanderbilt-Ingram Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Carmen C Solorzano, MD, FACS, Vanderbilt University Medical Center

Publications and helpful links

General Publications

• McWade MA, Paras C, White LM, Phay JE, Mahadevan-Jansen A, Broome JT. A novel optical approach to intraoperative detection of parathyroid glands. Surgery. 2013 Dec;154(6):1371-7; discussion 1377. doi: 10.1016/j.surg.2013.06.046.
• McWade MA, Sanders ME, Broome JT, Solorzano CC, Mahadevan-Jansen A. Establishing the clinical utility of autofluorescence spectroscopy for parathyroid detection. Surgery. 2016 Jan;159(1):193-202. doi: 10.1016/j.surg.2015.06.047. Epub 2015 Oct 9.
• Voelker R. Devices Help Surgeons See Parathyroid Tissue. JAMA. 2018 Dec 4;320(21):2193. doi: 10.1001/jama.2018.18768. No abstract available.
• Simental A, Ferris RL. Reoperative parathyroidectomy. Otolaryngol Clin North Am. 2008 Dec;41(6):1269-74, xii. doi: 10.1016/j.otc.2008.05.008.
• Cron DC, Kapeles SR, Andraska EA, Kwon ST, Kirk PS, McNeish BL, Lee CS, Hughes DT. Predictors of operative failure in parathyroidectomy for primary hyperparathyroidism. Am J Surg. 2017 Sep;214(3):509-514. doi: 10.1016/j.amjsurg.2017.01.012. Epub 2017 Jan 10.
• Doherty GM, Weber B, Norton JA. Cost of unsuccessful surgery for primary hyperparathyroidism. Surgery. 1994 Dec;116(6):954-7; discussion 957-8.
• Wachtel H, Cerullo I, Bartlett EK, Kelz RR, Karakousis GC, Fraker DL. What Can We Learn from Intraoperative Parathyroid Hormone Levels that Do Not Drop Appropriately? Ann Surg Oncol. 2015;22(6):1781-8. doi: 10.1245/s10434-014-4201-9. Epub 2014 Oct 30.
• Mohebati A, Shaha AR. Imaging techniques in parathyroid surgery for primary hyperparathyroidism. Am J Otolaryngol. 2012 Jul-Aug;33(4):457-68. doi: 10.1016/j.amjoto.2011.10.010. Epub 2011 Dec 7.
• Ahuja AT, Wong KT, Ching AS, Fung MK, Lau JY, Yuen EH, King AD. Imaging for primary hyperparathyroidism--what beginners should know. Clin Radiol. 2004 Nov;59(11):967-76. doi: 10.1016/j.crad.2004.04.005.
• Sosa JA, Powe NR, Levine MA, Udelsman R, Zeiger MA. Profile of a clinical practice: Thresholds for surgery and surgical outcomes for patients with primary hyperparathyroidism: a national survey of endocrine surgeons. J Clin Endocrinol Metab. 1998 Aug;83(8):2658-65. doi: 10.1210/jcem.83.8.5006.
• Chen H, Wang TS, Yen TW, Doffek K, Krzywda E, Schaefer S, Sippel RS, Wilson SD. Operative failures after parathyroidectomy for hyperparathyroidism: the influence of surgical volume. Ann Surg. 2010 Oct;252(4):691-5. doi: 10.1097/SLA.0b013e3181f698df.
• Novis DA, Zarbo RJ. Interinstitutional comparison of frozen section turnaround time. A College of American Pathologists Q-Probes study of 32868 frozen sections in 700 hospitals. Arch Pathol Lab Med. 1997 Jun;121(6):559-67.

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2020
• Primary Completion (Actual): March 3, 2023
• Study Completion (Actual): March 3, 2023

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 13, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Near Infrared Autofluorescence; Parathyroidectomy; Intraoperative Parathyroid Identification; Persistent Hyperparathyroidism; Persistent Hypercalcemia; Failed Parathyroidectomy; Repeat Parathyroidectomy
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Parathyroid Diseases; Head and Neck Neoplasms; Calcium Metabolism Disorders; Water-Electrolyte Imbalance; Hyperparathyroidism; Hyperparathyroidism, Primary; Adenoma; Hyperplasia; Parathyroid Neoplasms; Hypercalcemia
• Other Study ID Numbers: IRB 192486; 5R01CA212147-02 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Informed Consent Form and Clinical Study Report will be made available to other researchers as per the specified time-frame
• IPD Sharing Time Frame: Clinical Study Report will be shared 6 months after publication of trial data and will be available till end date of trial. Informed Consent Form will be shared for a year after the primary completion date of the trial.
• IPD Sharing Access Criteria: Request for Individual Patient Data (IPD) - Informed consent Form and Clinical Study Report - will be reviewed by the principal investigator of this clinical trial, before granting access to IPD
• IPD Sharing Supporting Information Type: ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes