Primary HyperparathyroidismCEUS-projectNCT04305561
Preoperative Localization Strategies in Primary Hyperparathyroidism
A study testing Contrast-enhanced ultrasound in people with Primary Hyperparathyroidism, run by Odense University Hospital at 1 site in Denmark.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Hyperparathyroidism
- What is being tested?
- Contrast-enhanced ultrasound
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 1 siteDenmark
- Study dates
- 5 Sep 2019to 31 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of CEUS With Conventional Ultrasound (US) to Dual-tracer 99mTcO4-/99mTc-MIBI Subtraction Scintigraphy With SPECT/CT for Localizing Pathological Parathyroid Glands in Patients With Primary Hyperparathyroidism
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.
Read the detailed description
The human body has four parathyroid glands. These are located in the neck at the backside of the thyroid gland. The four glands produce parathyroid hormone which regulates the amount of calcium in the blood. If one or more of the thyroid glands becomes hyperactive, too much parathyroid hormone is secreted into the blood. This condition is called hyperparathyroidism and results in elevated serum calcium levels. If left untreated, hyperparathyroidism may result in weak bones (osteoporosis), bone fractures, kidney stones and a myriad of unspecific symptoms.
In the vast majority of cases, only one of the four parathyroid glands is responsible for the disease, and the cure is surgical excision of the hyperactive gland. Such a surgery has traditionally involved a dissection of both sides of the neck, allowing the surgeon to visually inspect all four parathyroid glands to determine which gland(s) were hyperactive. Nowadays, if the hyperactive gland can be identified by parathyroid imaging prior to surgery, the surgeon can perform a minimally invasive procedure, focusing on the removal of a single gland. Such a focused procedure minimizes surgical risks and results in a shorter duration of surgery.
The parathyroid imaging regimen currently requires two out-patient visits on two separate days. The patient first visits the Department of Nuclear Medicine where a scan involving two radioactive tracers (a subtraction scintigraphy) and a 3D-examination (a SPECT/CT scan) are performed. The second visit takes place at the department of Head and Neck Surgery, where a head and neck surgeon performs an ultrasound examination of the neck.
The scans at the Department of Nuclear Medicine require the patient to lie completely still for a long time, expose the patient to some degree of radiation, and are relatively expensive. The ultrasound examination is fast and inexpensive, but isn't as sensitive as the scintigraphy (76% versus 70-92%).
Our project attempts to increase the sensitivity of the ultrasound examination by adding on an intravenous contrast agent. The contrast agent stays solely within the blood vessels, where it enhances the ultrasound signal. Contrast-enhanced ultrasound (CEUS) does not expose the patient to radiation, is fast to carry out, and the patient can be informed about the result of the scan immediately.
We hope that by introducing CEUS, we can change the order in which patients are examined prior to surgery, meaning that ultrasound - with or without an added contrast agent - will be the primary parathyroid imaging modality, and that patients will only continue to the Department of Nuclear Medicine if the result of the CEUS examination is uncertain.
Purpose
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.
Method
This will take the form of a prospective paired cohort study where patients receive a contrast-enhanced ultrasound examination in addition to the standard preoperative imaging regimen (subtraction scintigraphy with SPECT/CT and conventional ultrasound). The CEUS examiner will be blinded to the results of the subtraction scintigraphy and SPECT/CT. The surgeon will have access to the results of all the preoperative imaging procedures, including CEUS. Correct localization of a hyperactive parathyroid gland on preoperative imaging is confirmed by a histological examination of the surgical specimen.
- Conditions
- Primary Hyperparathyroidism
- Being tested
- Contrast-enhanced ultrasound
- Medical subject headings
- Hyperparathyroidism, Primary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Contrast-enhanced ultrasoundProcedure or surgery
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).
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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?
- Surgeon-performed conventional ultrasound
Measured: 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?
- Surgeon-performed conventional ultrasound combined with contrast-enhanced ultrasound (CEUS).
Measured: 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?
- Dual-tracer 99mTechnetium-pertechnetate/ 99mTechnetium-sestamibi subtraction scintigraphy (99mTcO4-/99mTc-MIBI) with single-photon emission computerised tomographic/CT fusion imaging (SPECT/CT).
Measured: No residual disease 6 months after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2020
- Study start5 Sep 2019
- Primary completion31 Dec 2021
- Study completion31 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary HyperparathyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Prospective paired cohort study.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 172 participants (actual)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sanne Høxbroe Michaelsen, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04305561
- Sponsor's protocol ID
- S-20190077
- Acronym
- CEUS-project
- Status last verified
- Apr 2022
- First submitted
- 24 Jan 2020
- Last updated
- 14 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 37052913
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of CEUS With Conventional Ultrasound (US) to Dual-tracer 99mTcO4-/99mTc-MIBI Subtraction Scintigraphy With SPECT/CT for Localizing Pathological Parathyroid Glands in Patients With Primary Hyperparathyroidism
- ClinicalTrials.gov ID
- NCT04305561
- Acronym / sponsor ID
- CEUS-project / S-20190077
- Conditions
- Primary Hyperparathyroidism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 172 participants (actual)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Study start
- 5 Sep 2019 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 31 Dec 2021 (actual)
- First posted
- 12 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The human body has four parathyroid glands. These are located in the neck at the backside of the thyroid gland. The four glands produce parathyroid hormone which regulates the amount of calcium in the blood. If one or more of the thyroid glands becomes hyperactive, too much parathyroid hormone is secreted into the blood. This condition is called hyperparathyroidism and results in elevated serum calcium levels. If left untreated, hyperparathyroidism may result in weak bones (osteoporosis), bone fractures, kidney stones and a myriad of unspecific symptoms.
In the vast majority of cases, only one of the four parathyroid glands is responsible for the disease, and the cure is surgical excision of the hyperactive gland. Such a surgery has traditionally involved a dissection of both sides of the neck, allowing the surgeon to visually inspect all four parathyroid glands to determine which gland(s) were hyperactive. Nowadays, if the hyperactive gland can be identified by parathyroid imaging prior to surgery, the surgeon can perform a minimally invasive procedure, focusing on the removal of a single gland. Such a focused procedure minimizes surgical risks and results in a shorter duration of surgery.
The parathyroid imaging regimen currently requires two out-patient visits on two separate days. The patient first visits the Department of Nuclear Medicine where a scan involving two radioactive tracers (a subtraction scintigraphy) and a 3D-examination (a SPECT/CT scan) are performed. The second visit takes place at the department of Head and Neck Surgery, where a head and neck surgeon performs an ultrasound examination of the neck.
The scans at the Department of Nuclear Medicine require the patient to lie completely still for a long time, expose the patient to some degree of radiation, and are relatively expensive. The ultrasound examination is fast and inexpensive, but isn't as sensitive as the scintigraphy (76% versus 70-92%).
Our project attempts to increase the sensitivity of the ultrasound examination by adding on an intravenous contrast agent. The contrast agent stays solely within the blood vessels, where it enhances the ultrasound signal. Contrast-enhanced ultrasound (CEUS) does not expose the patient to radiation, is fast to carry out, and the patient can be informed about the result of the scan immediately.
We hope that by introducing CEUS, we can change the order in which patients are examined prior to surgery, meaning that ultrasound - with or without an added contrast agent - will be the primary parathyroid imaging modality, and that patients will only continue to the Department of Nuclear Medicine if the result of the CEUS examination is uncertain.
Purpose
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.
Method
This will take the form of a prospective paired cohort study where patients receive a contrast-enhanced ultrasound examination in addition to the standard preoperative imaging regimen (subtraction scintigraphy with SPECT/CT and conventional ultrasound). The CEUS examiner will be blinded to the results of the subtraction scintigraphy and SPECT/CT. The surgeon will have access to the results of all the preoperative imaging procedures, including CEUS. Correct localization of a hyperactive parathyroid gland on preoperative imaging is confirmed by a histological examination of the surgical specimen.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
- Model description
- Prospective paired cohort study.
| Arm | Type | Receives |
|---|---|---|
| Ultrasound + Contrast-enhanced ultrasound | Other | Procedure: Contrast-enhanced ultrasoundPatients 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 |
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Contrast-enhanced ultrasoundUltrasound 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). | Procedure or surgery | Ultrasound + Contrast-enhanced ultrasound |
Primary outcome
Sensitivity of surgeon-performed conventional ultrasound
Time frame: No residual disease 6 months after surgery
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
Sensitivity of contrast-enhanced ultrasound
Time frame: No residual disease 6 months after surgery
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).
Sensitivity of radiation based imaging
Time frame: No residual disease 6 months after surgery
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).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2022.
- Derived from this study: PubMed 37052913Michaelsen 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Contrast-enhanced ultrasound in people with Primary Hyperparathyroidism, run by Odense University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity of surgeon-performed conventional ultrasound (time frame: No residual disease 6 months after surgery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04305561, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.