Preoperative Localization Strategies in Primary Hyperparathyroidism

NCT04305561 | Completed

• 1 other identifier: S-20190077
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this project is to examine, in a non-inferiority study, whether the combination of conventional ultrasound and contrast-enhanced ultrasound (CEUS) can replace the radiation-based imaging modalities that are currently used to localize pathological parathyroid glands prior to surgical removal in patients with primary hyperparathyroidism. This will take the form of a prospective paired cohort study where included patients receive a contrast-enhanced ultrasound examination in addition to the standard preoperative imaging regimen (subtraction scintigraphy with SPECT/CT and conventional ultrasound). Patients act as their own controls as all included patients undergo both CEUS and conventional imaging.

Conditions

Primary Hyperparathyroidism

Outcome Measures

Primary Outcomes (3)

• Sensitivity of surgeon-performed conventional ultrasound

  With the histopathological result of the surgically removed specimen(s) as the reference standard, what is the sensitivity, specificity, positive and negative predictive value of the following imaging modalities in localising pathological parathyroid glands to the correct side, quadrant, and Odense Classification? a. Surgeon-performed conventional ultrasound

  No residual disease 6 months after surgery

• Sensitivity of contrast-enhanced ultrasound

  With the histopathological result of the surgically removed specimen(s) as the reference standard, what is the sensitivity, specificity, positive and negative predictive value of the following imaging modalities in localising pathological parathyroid glands to the correct side, quadrant, and Odense Classification? b. Surgeon-performed conventional ultrasound combined with contrast-enhanced ultrasound (CEUS).

  No residual disease 6 months after surgery

• Sensitivity of radiation based imaging

  With the histopathological result of the surgically removed specimen(s) as the reference standard, what is the sensitivity, specificity, positive and negative predictive value of the following imaging modalities in localising pathological parathyroid glands to the correct side, quadrant, and Odense Classification? c. Dual-tracer 99mTechnetium-pertechnetate/ 99mTechnetium-sestamibi subtraction scintigraphy (99mTcO4-/99mTc-MIBI) with single-photon emission computerised tomographic/CT fusion imaging (SPECT/CT).

  No residual disease 6 months after surgery

Study Arms (2)

Ultrasound + Contrast-enhanced ultrasound

OTHER

Patients are offered a contrast-enhanced ultrasound (CEUS) examination in addition to conventional imaging. All included patients undergo both CEUS and conventional imaging, enabling them to act as their own controls. Pilot study: 60 patients Main study: 112 patients

Procedure: Contrast-enhanced ultrasound

Conventional imaging

NO INTERVENTION

Dual-tracer 99mTechnetium-pertechnetate/ 99mTechnetium-sestamibi subtraction scintigraphy with single-photon emission computerised tomographic/CT fusion imaging (SPECT/CT) combined with conventional ultrasound. Pilot study: 60 patients Main study: 112 patients

Interventions

Contrast-enhanced ultrasound PROCEDURE

Ultrasound contrast agent: Stabilized sulfur hexafluoride microbubbles (SonoVue®, Bracco). An 18 G needle will be placed in an antecubital vein and directly attached to a three-way stopcock with an extension tube. The SonoVue® will be prepared and shaken shortly before injection in accordance with the instructions provided in the product information leaflet. The patient will be injected with 1.2 ml SonoVue® at a pace of 1-2 ml/s using the 180 degree straight-flow channel of the three-way stopcock, directly followed by a 10 ml bolus of sodium chloride 9 mg/mL (0.9%) injected into the 90 degree channel of the three-way stopcock at a pace of approximately 2 ml/s. A full examination will typically require one to two injections of 1.2 ml of SonoVue® (one injection per suspected parathyroid adenoma).

Ultrasound + Contrast-enhanced ultrasound

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years and older with primary hyperparathyroidism (defined as an ionized calcium level above the upper reference level and a concomitant parathyroid hormone level in or above the upper third of the reference interval with no other known reason for the hyperparathyroid hypercalcemia) referred to the Department of ORL, Head and Neck Surgery at Odense University Hospital for parathyroidectomy.

You may not qualify if:

• Allergy to the contrast agent SonoVue®.
• Not legally competent.
• Does not read or speak Danish.
• Other causes of hypercalcemia (e.g. familial hypocalciuric hypercalcemia, pharmacologically or neoplastically induced hypercalcemia, secondary or tertiary hypercalcemia, uncontrolled hyperthyroidism, adrenal insufficiency, granulomatous diseases).
• Persistent or recurrent hyperparathyroidism.
• Previous surgery to the thyroid or the parathyroid glands.
• Current malignancy.
• Breastfeeding.
• Pregnancy.
• Contraindications to the use of SonoVue® (right-to-left shunts, severe pulmonary hypertension (pulmonary pressure \>90 mmHg), uncontrolled systemic hypertension, adult respiratory distress syndrome, recent acute coronary syndrome, clinically unstable ischaemic cardiac disease within the last seven days, severe heart rhythm disorders, acute heart failure, or chronic heart failure class III or IV according to the New York Heart Association).

Sponsors & Collaborators

• Odense University Hospital: lead

Study Sites (1)

Odense University Hospital

Odense C, 5000, Denmark

Location

Related Publications (1)

• Michaelsen SH, Bay M, Gerke O, Vestergaard S, Graumann O, Nielsen VE, Madsen AR, Bonnema SJ, Godballe C. Evaluation of Surgeon-Performed Ultrasonography With or Without Contrast Enhancement vs Scintigraphy in Patients With Primary Hyperparathyroidism. JAMA Otolaryngol Head Neck Surg. 2023 Jun 1;149(6):531-539. doi: 10.1001/jamaoto.2023.0389.

  PMID: 37052913 DERIVED

MeSH Terms

Conditions

Hyperparathyroidism, Primary

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Prospective paired cohort study.

Study Record Dates

• First Submitted: January 24, 2020
• First Posted: March 12, 2020
• Study Start: September 5, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)