Postoperative Hypoparathyroidism, Thyroid Cancer, Thyroid Neoplasms
Conditions
Keywords
Total Thyroidectomy, Intraoperative Parathyroid Identification, Near Infrared Autofluorescence, Postoperative Hypocalcemia, Postoperative Hypoparathyroidism
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 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
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.
Interventions
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.
Sponsors
National Cancer Institute (NCI)
Vanderbilt-Ingram Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Masking description
Only participants will be masked to the intervention.
Intervention 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).
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Number of Parathyroid Glands Identified With High Confidence Per Patient | Immediate. During total thyroidectomy procedure. | Average number of parathyroid glands identified (Experimental Group: Glands identified with naked eye + NIRAF; Control Group: Glands identified with naked eye) per patient |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Nights Spent in the Hospital After Total Thyroidectomy | 0 - 4 nights after total thyroidectomy | Number of nights spent in the hospital after the surgical procedure. 0 nights, 1 night, \>1 night |
| Number of Inadvertently Resected Parathyroid Glands | Intraoperatively or on histology (within 24 hours post operation) | Number of inadvertently resected parathyroid glands when parathyroid tissue is found in the resected thyroid specimens. |
| Postoperative Hypoparathyroidism/Hypocalcemia (Permanent) | 6 months after total thyroidectomy | If blood calcium has not normalized at 1st postsurgical clinical visit, total calcium level and/or PTH is subsequently measured as necessary. Patient is defined to have permanent hypoparathyroidism if PTH \< 16 pg/mL and/or activated Vitamin D is required to be symptom free at or after the 6th postoperative month. |
| Number of Auto-transplanted Parathyroid Glands | Immediate. During total thyroidectomy procedure. | Number of auto-transplanted parathyroid glands if the parathyroid gland was accidentally excised/devascularized. |
| Postoperative Hypoparathyroidism/Hypocalcemia (Immediate) | Within 24 hours after total thyroidectomy. | 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 |
| Number of Frozen Sections Sent for Analysis (of Suspected Parathyroid Tissue). | Immediate. During total thyroidectomy procedure. | Number of frozen sections sent for analysis during the procedure to confirm potential parathyroid tissue |
| Postoperative Hypoparathyroidism/Hypocalcemia (Transient) | 5 days to 6 months after total thyroidectomy. | 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 5-30 days after total thyroidectomy). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NIRAF Detection Technology + 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).
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. | 80 |
| 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 total thyroidectomy (TTx) with or without lymph node dissection (LND). | 80 |
| Total | 160 |
Baseline characteristics
| Characteristic | NIRAF Detection Technology + | NIRAF Detection Technology - | Total |
|---|---|---|---|
| Age, Continuous | 48.7 years STANDARD_DEVIATION 14.1 | 46.4 years STANDARD_DEVIATION 14.5 | 47.3 years STANDARD_DEVIATION 14.3 |
| Body Mass Index (BMI) | 31.9 kg/m2 STANDARD_DEVIATION 8.8 | 32.3 kg/m2 STANDARD_DEVIATION 8.4 | 32.1 kg/m2 STANDARD_DEVIATION 8.6 |
| Diagnosis Goiters and Nodular Diseases | 35 Participants | 31 Participants | 66 Participants |
| Diagnosis Graves' Diseases | 25 Participants | 25 Participants | 50 Participants |
| Diagnosis Thyroid Cancers | 20 Participants | 24 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 79 Participants | 78 Participants | 157 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Preoperative calcium (pg/dL) | 9.5 pg/dL STANDARD_DEVIATION 0.5 | 9.4 pg/dL STANDARD_DEVIATION 0.4 | 9.5 pg/dL STANDARD_DEVIATION 0.5 |
| Preoperative PTH (pg/mL) | 62.6 pg/mL STANDARD_DEVIATION 28 | 81.1 pg/mL STANDARD_DEVIATION 51.1 | 71.3 pg/mL STANDARD_DEVIATION 40 |
| Preoperative vitamin D (mcg) | 29.5 mcg STANDARD_DEVIATION 13 | 34.6 mcg STANDARD_DEVIATION 20.6 | 32 mcg STANDARD_DEVIATION 17.1 |
| Procedure Reoperation | 4 Participants | 3 Participants | 7 Participants |
| Procedure Total Thyroidectomy | 68 Participants | 65 Participants | 133 Participants |
| Procedure Total Thyroidectomy with Central Neck Dissection | 8 Participants | 12 Participants | 20 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black | 13 Participants | 17 Participants | 30 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 65 Participants | 62 Participants | 127 Participants |
| Region of Enrollment United States | 80 participants | 80 participants | 160 participants |
| Sex: Female, Male Female | 63 Participants | 61 Participants | 124 Participants |
| Sex: Female, Male Male | 17 Participants | 19 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 80 | 0 / 80 |
| other Total, other adverse events | 0 / 80 | 0 / 80 |
| serious Total, serious adverse events | 0 / 80 | 0 / 80 |
Outcome results
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
Time frame: Immediate. During total thyroidectomy procedure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NIRAF Detection Technology + | Average Number of Parathyroid Glands Identified With High Confidence Per Patient | 2.81 parathyroid glands | Standard Deviation 1.03 |
| NIRAF Detection Technology - | Average Number of Parathyroid Glands Identified With High Confidence Per Patient | 2.75 parathyroid glands | Standard Deviation 0.95 |
p-value: 0.6905t-test, 2 sided
Secondary
Number of Auto-transplanted Parathyroid Glands
Number of auto-transplanted parathyroid glands if the parathyroid gland was accidentally excised/devascularized.
Time frame: Immediate. During total thyroidectomy procedure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NIRAF Detection Technology + | Number of Auto-transplanted Parathyroid Glands | 43 parathyroid glands |
| NIRAF Detection Technology - | Number of Auto-transplanted Parathyroid Glands | 39 parathyroid glands |
Secondary
Number of Frozen Sections Sent for Analysis (of Suspected Parathyroid Tissue).
Number of frozen sections sent for analysis during the procedure to confirm potential parathyroid tissue
Time frame: Immediate. During total thyroidectomy procedure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NIRAF Detection Technology + | Number of Frozen Sections Sent for Analysis (of Suspected Parathyroid Tissue). | 0.08 frozen sections | Standard Deviation 0.4 |
| NIRAF Detection Technology - | Number of Frozen Sections Sent for Analysis (of Suspected Parathyroid Tissue). | 0.1 frozen sections | Standard Deviation 0.3 |
Secondary
Number of Inadvertently Resected Parathyroid Glands
Number of inadvertently resected parathyroid glands when parathyroid tissue is found in the resected thyroid specimens.
Time frame: Intraoperatively or on histology (within 24 hours post operation)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NIRAF Detection Technology + | Number of Inadvertently Resected Parathyroid Glands | 0.09 parathyroid glands | Standard Deviation 0.3 |
| NIRAF Detection Technology - | Number of Inadvertently Resected Parathyroid Glands | 0.06 parathyroid glands | Standard Deviation 0.2 |
Secondary
Number of Nights Spent in the Hospital After Total Thyroidectomy
Number of nights spent in the hospital after the surgical procedure. 0 nights, 1 night, \>1 night
Time frame: 0 - 4 nights after total thyroidectomy
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| NIRAF Detection Technology + | Number of Nights Spent in the Hospital After Total Thyroidectomy | 0 Nights | 1 Participants |
| NIRAF Detection Technology + | Number of Nights Spent in the Hospital After Total Thyroidectomy | 1 Night | 77 Participants |
| NIRAF Detection Technology + | Number of Nights Spent in the Hospital After Total Thyroidectomy | > 1 Night | 2 Participants |
| NIRAF Detection Technology - | Number of Nights Spent in the Hospital After Total Thyroidectomy | 0 Nights | 4 Participants |
| NIRAF Detection Technology - | Number of Nights Spent in the Hospital After Total Thyroidectomy | 1 Night | 72 Participants |
| NIRAF Detection Technology - | Number of Nights Spent in the Hospital After Total Thyroidectomy | > 1 Night | 4 Participants |
Secondary
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
Time frame: Within 24 hours after total thyroidectomy.
Population: 1 participant did not have their labs completed until 5-14 days post-operation.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NIRAF Detection Technology + | Postoperative Hypoparathyroidism/Hypocalcemia (Immediate) | 19 Participants |
| NIRAF Detection Technology - | Postoperative Hypoparathyroidism/Hypocalcemia (Immediate) | 16 Participants |
Secondary
Postoperative Hypoparathyroidism/Hypocalcemia (Permanent)
If blood calcium has not normalized at 1st postsurgical clinical visit, total calcium level and/or PTH is subsequently measured as necessary. Patient is defined to have permanent hypoparathyroidism if PTH \< 16 pg/mL and/or activated Vitamin D is required to be symptom free at or after the 6th postoperative month.
Time frame: 6 months after total thyroidectomy
Population: Only participants with at least 6-months of follow-up were included in this analysis. The majority of follow-ups for thyroid surgery occured nat 5-14 days post-operation and most people do not return for longer follow-up unless they have on-going abnormal labs after that mark.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NIRAF Detection Technology + | Postoperative Hypoparathyroidism/Hypocalcemia (Permanent) | 0 Participants |
| NIRAF Detection Technology - | Postoperative Hypoparathyroidism/Hypocalcemia (Permanent) | 0 Participants |
Secondary
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 5-30 days after total thyroidectomy).
Time frame: 5 days to 6 months after total thyroidectomy.
Population: Not all of the patients come back for follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NIRAF Detection Technology + | Postoperative Hypoparathyroidism/Hypocalcemia (Transient) | 3 Participants |
| NIRAF Detection Technology - | Postoperative Hypoparathyroidism/Hypocalcemia (Transient) | 5 Participants |