Evaluating Impact of NIRAF Detection for Identifying Para... | NCT04299425

NCT04299425

ID	Type	Description	Link
5R01CA212147-02	U.S. NIH Grant/Contract		View source

Status Module

Sponsor/Collaborators Module

Name	Class
National Cancer Institute (NCI)	NIH

Oversight Module

Description Module

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.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
NIRAF Detection Technology +	Experimental	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
NIRAF Detection Technology -	No Intervention	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).

Interventions

Name	Type	Description	Arm Group Labels	Other Names
NIRAF Detection Technology	Device	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.

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Carmen C Solorzano, MD, FACS	Vanderbilt University Medical Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Vanderbilt University Medical Center		Nashville	Tennessee	37212	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
19040985	Background	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.
28108069	Background	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.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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). 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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

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	Dec 8, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	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). 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.
BG001	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).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00080 BG00180 BG002160

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00056.8± 14.6 BG00159.8± 14.4 BG00258.3± 14.5

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00062 BG00163 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG00073 BG00174 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

Non-Hispanic

Title	Measurements
	BG00079 BG00180 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00080 BG00180 BG002

Body Mass Index (BMI)

Mean

Standard Deviation

kg/m2

Title

Denominators

Categories

Title	Measurements
	BG00030.77± 7.52 BG00130.94± 7.72 BG002

Diagnosis

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Primary sporadic HPT	BG00072 BG00171 BG002

Preoperative calcium (pg/dL)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG00011.115± 0.689 BG00111.112± 0.712 BG002

Preoperative PTH (pg/mL)

Mean

Standard Deviation

pg/mL

Title

Denominators

Categories

Title	Measurements
	BG000152.3± 79.8 BG001163.6± 139 BG002

Preoperative vitamin D

Mean

Standard Deviation

mcg

Title

Denominators

Categories

Title	Measurements
	BG00036.7± 16 BG00139.6± 20.5 BG002

Procedure by intention

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Focused	BG00027 BG00124 BG002

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

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

Posted

Mean

Standard Deviation

parathyroid glands

Immediate. During PTx procedure.

ID	Title	Description
OG000	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). 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.
OG001	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).

Units	Counts
Participants	OG00080 OG00180

Title

Denominators

Categories

Title	Measurements
	OG0003.1± 1.21 OG0012.7± 1.13

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		t-test, 2 sided		0.04														Superiority

Secondary

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.

Posted

Count of Participants

Participants

6 months after PTx procedure

ID	Title	Description
OG000	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). 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.
OG001

Secondary

Number of Frozen Sections Sent for Analysis

Number of frozen sections sent for analysis during the procedure to confirm potential parathyroid tissue

Posted

Number

frozen sections

Immediate. During PTx procedure.

ID	Title	Description
OG000	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). 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.
OG001	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).

Secondary

Duration of Parathyroidectomy (PTx) Procedure

Duration of PTx procedure - timed from skin incision until the surgeon notifies the anesthesia team to awaken the patient

Posted

Mean

Standard Deviation

minutes

Immediate. During PTx procedure.

ID	Title	Description
OG000	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). 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.
OG001	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).

Secondary

Number of Participants Stratified by Duration of Hospital Stay

Number of nights spent for postoperative recovery in the hospital after the surgical procedure.

Posted

Count of Participants

Participants

0-72 hours after PTx procedure.

ID	Title	Description
OG000	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). 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.
OG001	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).

Secondary

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

Only the NIRAF Detection Technology + arm was included in the analysis to calculate the rate of false positives by the device. Since the NIRAF Detection Technology - did not use the device that arm was not included.

Posted

Number

false positives

Immediate to 10 days after PTx procedure.

ID	Title	Description
OG000	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). 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.

Secondary

Number of Patients Who Have Had Repeat Parathyroidectomy (PTx) Procedure

Number of patients with repeat PTx procedure performed after the current procedure.

Nearly all patients attended their first follow-up appointment (5-14 days post-operation), however about 30 patients were lost for long-term follow-up.

Posted

Count of Participants

Participants

At 6-months post-operation

ID	Title	Description
OG000	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). 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.
OG001	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).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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). 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.	0	80	0	80	0	80
EG001	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).	0	80	0	80	0	80

Only 63% of the cohort had follow-up for 6-months or longer, which may underestimate the rate of failure. The relatively small sample size may miss rare events such as operative failure. Additionally, inter-variability amongst the two surgeons and their surgical approaches adds more complexity. Lastly, these findings may only be generalizable to higher volume centers with more experienced surgeons.

Certain Agreements

First MCP Posted Date

ID	Term
D010282	Parathyroid Neoplasms
D006934	Hypercalcemia
D049950	Hyperparathyroidism, Primary

Ancestor Terms

ID	Term
D004701	Endocrine Gland Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D006258	Head and Neck Neoplasms
D004700	Endocrine System Diseases
D010279	Parathyroid Diseases
D002128	Calcium Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D014883	Water-Electrolyte Imbalance
D006961	Hyperparathyroidism