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

Primary Purpose

Parathyroid Adenoma, Parathyroid Neoplasms, Parathyroid Hyperplasia

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
NIRAF Detection Technology
Sponsored by
Vanderbilt-Ingram Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Parathyroid Adenoma focused on measuring Parathyroidectomy, Intraoperative Parathyroid Identification, Near Infrared Autofluorescence, Persistent Hyperparathyroidism, Persistent Hypercalcemia, Failed Parathyroidectomy, Repeat Parathyroidectomy

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

NIRAF Detection Technology +

NIRAF Detection Technology -

Arm Description

Parathyroid gland identification will be performed with PTeye using NIRAF detection technology as an adjunctive tool in patients who undergo parathyroidectomy (PTx).

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).

Outcomes

Primary Outcome Measures

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).
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.
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.

Secondary Outcome Measures

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)
Number of parathyroid glands identified with NIRAF
Number of parathyroid glands identified with NIRAF, which was not seen with surgeon's naked eye
Number of frozen sections sent for analysis
Number of frozen sections sent for analysis during the procedure to confirm potential parathyroid tissue
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
Number of intra-operative parathyroid hormone (PTH) assays sent
Number of intra-operative parathyroid hormone assays sent during the 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.
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.
Duration of parathyroidectomy (PTx) procedure
Duration of PTx procedure - timed from skin incision until the surgeon notifies the anesthesia team to awaken the patient
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.
Number of nights spent in the hospital after parathyroidectomy
Number of nights spent for postoperative recovery in the hospital after the surgical 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
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
Number of patients who have had repeat parathyroidectomy (PTx) procedure
Number of patients with repeat PTx procedure performed after the current procedure

Full Information

First Posted
March 4, 2020
Last Updated
February 7, 2023
Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT04299425
Brief Title
Evaluating Impact of NIRAF Detection for Identifying Parathyroid Glands During Parathyroidectomy
Acronym
NIRAF
Official Title
Evaluating Impact of Near Infrared Autofluorescence (NIRAF) Detection for Identifying Parathyroid Glands During Parathyroidectomy
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 13, 2020 (Actual)
Primary Completion Date
October 30, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt-Ingram Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parathyroid Adenoma, Parathyroid Neoplasms, Parathyroid Hyperplasia, Parathyroid Cancer, Hypercalcemia, Primary Hyperparathyroidism
Keywords
Parathyroidectomy, Intraoperative Parathyroid Identification, Near Infrared Autofluorescence, Persistent Hyperparathyroidism, Persistent Hypercalcemia, Failed Parathyroidectomy, Repeat Parathyroidectomy

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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
Participant
Masking Description
Only participants will be masked to the intervention.
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NIRAF Detection Technology +
Arm Type
Experimental
Arm Description
Parathyroid gland identification will be performed with PTeye using NIRAF detection technology as an adjunctive tool in patients who undergo parathyroidectomy (PTx).
Arm Title
NIRAF Detection Technology -
Arm Type
No Intervention
Arm Description
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).
Intervention Type
Device
Intervention Name(s)
NIRAF Detection Technology
Other Intervention Name(s)
PTeye Device
Intervention Description
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.
Primary Outcome Measure Information:
Title
Persistent hyperparathyroidism (Immediate)
Description
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).
Time Frame
During parathyroidectomy (PTx) procedure
Title
Persistent hyperparathyroidism or hypercalcemia (transient)
Description
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.
Time Frame
5-14 days after PTx procedure
Title
Persistent hyperparathyroidism or hypercalcemia (failed parathyroidectomy)
Description
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.
Time Frame
6 months after PTx procedure
Secondary Outcome Measure Information:
Title
Overall number of parathyroid glands identified
Description
Overall number of parathyroid glands identified (Experimental Group: Glands identified with naked eye + NIRAF; Control Group: Glands identified with naked eye)
Time Frame
Immediate. During PTx procedure.
Title
Number of parathyroid glands identified with NIRAF
Description
Number of parathyroid glands identified with NIRAF, which was not seen with surgeon's naked eye
Time Frame
Immediate. During PTx procedure.
Title
Number of frozen sections sent for analysis
Description
Number of frozen sections sent for analysis during the procedure to confirm potential parathyroid tissue
Time Frame
Immediate. During PTx procedure.
Title
Number of diseased parathyroid glands identified versus preoperatively localized glands
Description
Number of diseased parathyroid glands identified intra-operatively versus glands localized preoperatively using sestamibi, CT or ultrasound
Time Frame
Preoperative to immediate during PTx procedure.
Title
Number of intra-operative parathyroid hormone (PTH) assays sent
Description
Number of intra-operative parathyroid hormone assays sent during the procedure
Time Frame
Immediate. During PTx procedure.
Title
Duration taken to identify first parathyroid gland
Description
Duration taken to identify 1st parathyroid gland in PTx procedure - timed from skin incision to finding PG.
Time Frame
Immediate. During PTx procedure.
Title
Duration taken to identify last parathyroid gland
Description
Duration taken to identify last parathyroid gland in PTx procedure - timed from skin incision to finding the last PG.
Time Frame
Immediate. During PTx procedure.
Title
Duration of parathyroidectomy (PTx) procedure
Description
Duration of PTx procedure - timed from skin incision until the surgeon notifies the anesthesia team to awaken the patient
Time Frame
Immediate. During PTx procedure.
Title
Duration taken for intraoperative parathyroid hormone (PTH) to normalize
Description
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.
Time Frame
Immediate. During PTx procedure.
Title
Number of nights spent in the hospital after parathyroidectomy
Description
Number of nights spent for postoperative recovery in the hospital after the surgical procedure.
Time Frame
0-72 hours after PTx procedure.
Title
Number of 'false positive' tissues excised by surgeon
Description
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
Time Frame
Immediate to 10 days after PTx procedure.
Title
Number of doctor visits/emergency department visits or hospital admissions
Description
Number of doctor visits/emergency department visits or hospital admissions due to persistent hypercalcemia and/or associated symptoms after parathyroidectomy procedure
Time Frame
Up to 6 months after PTx procedure.
Title
Number of patients who have had repeat parathyroidectomy (PTx) procedure
Description
Number of patients with repeat PTx procedure performed after the current procedure
Time Frame
6 - 12 months after PTx procedure.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Carmen C Solorzano, MD, FACS
Organizational Affiliation
Vanderbilt University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
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19040985
Citation
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PubMed Identifier
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Evaluating Impact of NIRAF Detection for Identifying Parathyroid Glands During Parathyroidectomy

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