Description

STUDY COMPONENTS AND DEVICE The investigational platform is a modified Meta Quest head-mounted stereoscopic goggle system configured for label-free near-infrared autofluorescence (NIRAF) imaging, with excitation at approximately 780 nm and detection of parathyroid autofluorescence near 800 nm. No injected contrast agent is used. NIRAF supplements surgical anatomy and clinical judgment; fluorescence does not by itself establish tissue identity, vascular viability, or preserved endocrine function.

Component A is a nonrandomized, 30-participant ex vivo specimen-imaging and pathology-validation component. NIRAF-positive foci on clinically removed thyroidectomy specimens are mapped and correlated with pathology. Available preoperative, early postoperative, and approximately two-month laboratory data are summarized descriptively. Component A participants are not included in the randomized efficacy analysis. No retained parathyroid gland is biopsied for research.

Component B has a fixed target of 250 randomized adults undergoing total or completion thyroidectomy, allocated 1:1 to standard surgery or standard surgery plus NIRAF. This is a feasibility-constrained sample size; detectable effects depend on the actual frequency of the primary outcome. Enrollment in Component A is additional to the randomized target, giving an overall planned enrollment of 280. Participant attribution and analyses follow contemporaneous enrollment records and applicable protocol versions. Revised assessments and outcome definitions will take effect after documented ethics approval of the amendment and from the recorded implementation date. Previously enrolled participants remain accounted for under their applicable protocol versions. Earlier observations are not relabeled as prospectively collected under the revision, and the original outcomes and amendment history will be reported transparently.

OPERATIVE WORKFLOW Both groups receive the same surgeon-led preservation principles, training standards, criteria for conventional rescue/autotransplantation, and postoperative endocrine management. Allocation is concealed until assignment, and the analysis accounts for operating surgeon. In both groups, the surgeon records the glands identified under white light, their locations, confidence in identification, and the intended operative action before the assigned additional assessment. A brief white-light reassessment is performed in the control group and a brief NIRAF assessment at the corresponding surgical stage in the intervention group, early enough to inform preservation before irreversible dissection. Extra dissection solely to find every gland is not required.

In the intervention group, NIRAF imaging of the removed specimen can identify suspected excised parathyroid tissue. Rescue/autotransplantation is performed only when clinically appropriate and oncologically safe. The control group receives standard white-light assessment and conventional rescue when indicated; experimental NIRAF specimen imaging does not guide control-group care. Removed tissue is processed using comparable pathology procedures in both groups. Distinct glands and tissue fragments are recorded separately, together with the reason for removal.

RANDOMIZED CLINICAL OUTCOMES AND FOLLOW-UP The primary outcome is early biochemical hypoparathyroidism, defined as serum intact PTH below the testing laboratory's assay-specific lower limit of normal at 12 to 24 hours after completion of skin closure, targeting 18 hours, regardless of concurrent calcium or symptoms. Before the revised assessments begin, the site documents the testing laboratory, intact PTH assay, units, reference interval, calcium interpretation method, and common management algorithm in the study laboratory/endocrine manual. The assay-specific lower limit of normal is used identically in both randomized groups; no universal numeric PTH cutoff or assay manufacturer is imposed by this registry entry. Any subsequent assay or reference-range change is documented and addressed in the analysis plan. If more than one valid sample is available within the window, the sample closest to 18 hours is used; ties use the earlier sample. A missing in-window sample is not classified as a normal result. Earlier clinically indicated tests do not replace this primary sample.

Five scheduled research blood collections are performed: baseline 1 to 2 days before surgery; 12 to 24 hours after skin closure; day 42 plus or minus 7 days; day 90 plus or minus 14 days; and day 180 plus or minus 21 days. The core panel is intact PTH, total calcium, and albumin. Baseline and six-month panels additionally include magnesium, phosphate, creatinine with estimated glomerular filtration rate, and 25-hydroxyvitamin D. Routine clinical samples meeting these timing and assay requirements can also serve as study samples. No separate routine research blood draw is required at two or four weeks.

A safety assessment occurs at 48 to 72 hours by telephone after discharge or through routine inpatient review. Patients with low PTH, low calcium, symptoms, or replacement treatment receive additional assessment and testing under the common clinical algorithm; they do not wait until the six-week research visit. Day 0 to 30 events are ascertained from records and patient confirmation, which may be completed at the six-week visit. Medication starts, stops, doses, indications, and adherence between visits are recorded. Necessary treatment is never delayed or withheld for research sampling.

The key secondary outcome is biochemical hypoparathyroidism at six weeks, using the same PTH threshold in all randomized participants. Other outcomes include therapeutic active-vitamin-D and oral-calcium treatment days during postoperative days 1 to 90; biochemical and symptomatic hypocalcemia; intravenous calcium and hypocalcemia-related acute-care use; parathyroid tissue excision and autotransplantation; operative time; and surgical or device-related adverse events.

Endocrine status is assessed at three and six months using standardized records reviewed without treatment allocation. Documented normal function or recovery requires PTH and albumin-adjusted calcium within their reference ranges after at least 14 consecutive days without active vitamin D or therapeutic calcium. This is an operational study assessment rule. Treatment withdrawal is attempted only when clinically safe under endocrine supervision; continued prescribing alone does not establish ongoing disease. Cases are classified as documented normal function/recovery, ongoing dysfunction, or indeterminate. Recovery among participants with earlier abnormal findings is reported separately. Dysfunction at six months is not labeled permanent hypoparathyroidism.

DEVICE-PERFORMANCE ASSESSMENT Consecutive goggle-assisted operations are assessed, including procedures with no additional finding and device failures. The principal device-performance measure is the proportion of participants with at least one additional clinically adjudicated parathyroid gland identified beyond the recorded initial white-light assessment. Counts of additional glands are also reported. In situ identity is clinically adjudicated; pathology confirmation is used when tissue has been removed for clinical reasons. Specimen pathology validation is not treated as histological confirmation of every gland preserved in situ.

A clinically significant event (CSE) is new or corrected NIRAF information leading to a documented clinically meaningful change in operative management. Prespecified categories include a change in dissection to preserve a newly identified gland, a corrected tissue identification that changes management, or clinically indicated rescue/autotransplantation after specimen detection. Additional fluorescence or increased confidence without a management change is not, by itself, a CSE. Pre-imaging findings and intended actions, subsequent findings, changed actions or no change, and final gland disposition are documented using operative records and available images, video, and pathology. Independent review applies the prespecified criteria without postoperative endocrine outcomes where feasible. Patient-level CSE proportions and event counts by type are reported; a preservation-related CSE is not interpreted as proof of preserved gland function or prevented hypoparathyroidism.

ANALYSIS AND REPORTING Randomized clinical analyses follow intention to treat, retaining device failures and crossovers in their assigned groups, with prespecified handling of missing outcomes. The primary comparison uses a two-sided 0.05 significance level. The six-week key secondary outcome is tested confirmatorily only if the primary comparison is significant; other outcomes are supportive and reported with effect estimates and confidence intervals. Device-performance reporting is distinct from randomized endocrine efficacy reporting, and publications identify any overlapping participants and protocol versions. An early device report does not constitute a definitive interim test of clinical efficacy. The statistical analysis plan specifies amendment-era handling before further treatment-arm outcome review.