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Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism

Primary Purpose

Primary Aldosteronism, Aldosterone-Producing Adenoma

Status
Recruiting
Phase
Not Applicable
Locations
Norway
Study Type
Interventional
Intervention
EUS-RFA of left adrenal gland
adrenalectomy
Sponsored by
Haukeland University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Aldosteronism focused on measuring radio frequency ablation, postoperative hypoaldosteronism, postoperative hypocortisolism

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18 to 60 years
  • Signed written informed consent
  • PA diagnosis confirmed according to Endocrine Society PA Guideline criteria
  • AVS lateralisation to one adrenal (lateralisation index ≥ 4,0)
  • If CT scan shows an adrenal nodule to the same adrenal as AVS lateralisation result: nodule size < 4 cm and enhancement criteria for adrenal adenoma (native hounsfield units < 10 or relative wash-out > 40% or absolute wash-out > 60%)
  • For EUS-RFA group: AVS lateralisation to the left adrenal only and EUS-guided tissue sampling of detected adrenal tumour for morphologic and functional characterisation confirming benign tumour tissue with aldosterone-producing cells

Exclusion Criteria:

  • Age <18 or > 60 years
  • CT scan or histological suspicion of adrenal malignancy
  • Patient refusal to undergo either EUS-RFA or adrenalectomy

Sites / Locations

  • Haukeland University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

EUS-RFA of left adrenal gland treatment group

Adrenalectomy control group

Arm Description

PA patients with AVS-confirmed lateralisation to the left adrenal and consent for EUS-RFA, will have a first EUS performed. If EUS identifies an adrenal nodule in the left adrenal, an EUS-guided fine needle tissue sampling will be performed of the adenoma/nodule and of adjacent non-adenoma adrenal tissue. If the tissue sampling confirms benign aldosterone-producing cells in the adenoma, a subsequent EUS-RFA treatment procedure will be performed.

Patients with AVS lateralisation to the left adrenal gland with EUS performed but no visible tumour found by EUS or EUS-guided tissue sampling not showing benign aldosterone-producing cells, therefore not suitable for RFA treatment, will be treated with conventional unilateral left adrenalectomy and will be included in an adrenalectomy control group. Patients with AVS lateralisation to the left adrenal but not consenting to EUS, and patients with AVS lateralisation to the right adrenal, will all likewise be treated with conventional unilateral adrenalectomy, and included in the adrenalectomy control group

Outcomes

Primary Outcome Measures

Biochemical outcome after EUS-RFA compared with unilateral adrenalectomy
Biochemical outcome will be evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 3 months
Biochemical outcome after EUS-RFA compared with unilateral adrenalectomy
Biochemical outcome will be re-evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 1 year
Clinical outcome after EUS-RFA compared with unilateral adrenalectomy
Clinical outcome will be evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 1 year

Secondary Outcome Measures

Number of participants with procedural complications of EUS-RFA compared with unilateral adrenalectomy
Procedural complications of EUS-RFA compared with unilateral adrenalectomy will be performed using the Clavien-Dindo classification.
Length of hospital stay after EUS-RFA compared with after adrenalectomy
Length of hospital stay after EUS-RFA will be compared with adrenalectomy, and will be evaluated at follow-up after 3 months
Number of participants with postoperative hypoaldosteronism
Number of participants with postoperative hypoaldosteronism after EUS-RFA will be compared with unilateral adrenalectomy by biochemical assessment at 3 months after treatment
Number of participants with postoperative hypocortisolism
Number of participants with postoperative hypocortisolism after EUS-RFA will be compared with unilateral adrenalectomy. In patients with an abnormal pre-treatment 1 mg dexamethasone suppression test or a low morning cortisol < 300 nmol/L after RFA or adrenalectomy, individual advise of cortisone acetate replacement therapy will be given and an stimulation adrenocorticotropic hormone (ACTH) test will be performed in the Endocrinology Out-patient clinic ~ 6 weeks of discharge
Change from baseline in health-related quality of life at 1 year
Change in health-related quality of life after treatment compared with pre-treatment, will be measured by the validated RAND-36 Health Survey, and will be compared in the EUS-RFA group and adrenalectomy group. All participants will fill out a RAND-36 form prior to treatment, and repeated 1 year after treatment

Full Information

First Posted
May 2, 2022
Last Updated
September 22, 2023
Sponsor
Haukeland University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05368090
Brief Title
Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism
Official Title
Endoscopic Ultrasound-guided Radiofrequency Ablation as a Novel Treatment Option Compared With Adrenalectomy in Left-sided Primary Aldosteronism
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 3, 2022 (Actual)
Primary Completion Date
December 31, 2028 (Anticipated)
Study Completion Date
December 31, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Haukeland University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study, the investigators will compare endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) treatment in patients with primary aldosteronism (PA) with lateralisation of their aldosterone overproduction to their left adrenal and a left-sided tumour visible by EUS, with conventional unilateral adrenalectomy. The primary objective of the study is to evaluate biochemical and clinical outcome after EUS-RFA treatment compared with unilateral adrenalectomy. Secondary objectives are to compare safety/procedural complications of the two procedures, length of hospital stay, rate of postoperative hypoaldosteronism and hypocortisolism after treatment, and change health-related quality of life compared with pre-treatment.
Detailed Description
Primary aldosteronism (PA) is the most common cause of secondary hypertension, and is associated with worse cardiovascular outcome than primary hypertension. Early diagnosis and treatment is paramount to avoid excess morbidity and death. The two main forms of PA are unilateral aldosterone-producing adenoma (APA), and bilateral idiopathic hyperaldosteronism (IHA). Differentiation between unilateral and bilateral disease determines treatment options. Adrenal vein sampling is the recommended procedure to determine PA subtype, unilateral or bilateral. For unilateral APAs, surgery with unilateral adrenalectomy is recommended treatment. Unilateral PA caused by an APA may also be treated with new, less invasive treatment modalities such as radiofrequency ablation (RFA), treating the APA only and sparing the remaining adrenal. The left adrenal is situated in near proximity to the stomach and is easily reached by endoscopic ultrasound (EUS), and may be targeted for RFA. In this study, EUS-RFA treatment in PA patients with adrenal vein sampling (AVS) lateralisation to the left adrenal and a visible adrenal tumour detected by EUS, will be compared with conventional unilateral adrenalectomy. Patients aged 18-60 years diagnosed with PA with AVS lateralisation to the left adrenal will be asked for study inclusion in the EUS-RFA group. If CT scan shows an adrenal nodule to the left adrenal, nodule size must be < 40 mm and enhancement value must fulfill criteria for a benign adenoma. Patients consenting to the EUS-RFA group will have a first EUS performed. If EUS of the left adrenal identifies an adrenal nodule, a fine needle tissue sampling will be performed for morphological and functional characterisation, including application of specific imaging mass cytometry for detection of aldosterone-producing cells. If the tumour tissue sampling confirms benign aldosterone-producing cells, a subsequent EUS-guided RFA procedure of the tumour will be performed. Patients not eligible for RFA treatment after the initial EUS will be treated with adrenalectomy. These patients will be included in an adrenalectomy control group, together with patients not consenting to EUS-RFA, and PA patients with lateralisation to the right adrenal, all performing adrenalectomy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Aldosteronism, Aldosterone-Producing Adenoma
Keywords
radio frequency ablation, postoperative hypoaldosteronism, postoperative hypocortisolism

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Two study groups: one study group will perform endoscopic ultrasounded-guided radiofrequency ablation treatment of an left adrenal tumour in patients with left-sided unilateral primary aldosteronism. A control group will consist of patients with unilateral primary aldosteronism (left or right) undergoing conventional unilateral adrenalectomy.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
EUS-RFA of left adrenal gland treatment group
Arm Type
Experimental
Arm Description
PA patients with AVS-confirmed lateralisation to the left adrenal and consent for EUS-RFA, will have a first EUS performed. If EUS identifies an adrenal nodule in the left adrenal, an EUS-guided fine needle tissue sampling will be performed of the adenoma/nodule and of adjacent non-adenoma adrenal tissue. If the tissue sampling confirms benign aldosterone-producing cells in the adenoma, a subsequent EUS-RFA treatment procedure will be performed.
Arm Title
Adrenalectomy control group
Arm Type
Active Comparator
Arm Description
Patients with AVS lateralisation to the left adrenal gland with EUS performed but no visible tumour found by EUS or EUS-guided tissue sampling not showing benign aldosterone-producing cells, therefore not suitable for RFA treatment, will be treated with conventional unilateral left adrenalectomy and will be included in an adrenalectomy control group. Patients with AVS lateralisation to the left adrenal but not consenting to EUS, and patients with AVS lateralisation to the right adrenal, will all likewise be treated with conventional unilateral adrenalectomy, and included in the adrenalectomy control group
Intervention Type
Procedure
Intervention Name(s)
EUS-RFA of left adrenal gland
Intervention Description
Patients will fast, receive prophylactic antibiotics and conscious sedation prior to the procedure.The procedure is performed with a standard linear echo-endoscope with a 3.7 mm or larger working channel. The left adrenal is identified from the fundus of the stomach. Color-Doppler is used to map adrenal vascularity. Ultrasound contrast is used to demarcate the border of the tumour. The RFA ablation catheter is water-cooled and stable temperature is maintained at 70-75 degrees celsius until formation of heat bubbles can be seen on EUS. If necessary, the procedure is repeated after moving the probe until the whole adenoma volume is ablated. Ultrasound contrast medium is used after the procedure to ensure that the target for the ablation is non vascularized, before termination. The patients will be observed at the postoperative unit a few hours, and further in the ward for 24h
Intervention Type
Procedure
Intervention Name(s)
adrenalectomy
Intervention Description
Patients in the adrenalectomy group will be admitted in the Dept. of Endocrine surgery. They will undergo laparoscopic transabdominal total adrenalectomy according to routine. The patients will be monitored in the postoperative unit 4-6 hours before returning to the ward. If no complications occur, the patients are usually discharged day 2 after surgery.
Primary Outcome Measure Information:
Title
Biochemical outcome after EUS-RFA compared with unilateral adrenalectomy
Description
Biochemical outcome will be evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 3 months
Time Frame
3 months
Title
Biochemical outcome after EUS-RFA compared with unilateral adrenalectomy
Description
Biochemical outcome will be re-evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 1 year
Time Frame
1 year
Title
Clinical outcome after EUS-RFA compared with unilateral adrenalectomy
Description
Clinical outcome will be evaluated by international standardised "Primary aldosteronism surgery outcome" (PASO) criteria at follow-up visits after 1 year
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Number of participants with procedural complications of EUS-RFA compared with unilateral adrenalectomy
Description
Procedural complications of EUS-RFA compared with unilateral adrenalectomy will be performed using the Clavien-Dindo classification.
Time Frame
3 months
Title
Length of hospital stay after EUS-RFA compared with after adrenalectomy
Description
Length of hospital stay after EUS-RFA will be compared with adrenalectomy, and will be evaluated at follow-up after 3 months
Time Frame
3 months
Title
Number of participants with postoperative hypoaldosteronism
Description
Number of participants with postoperative hypoaldosteronism after EUS-RFA will be compared with unilateral adrenalectomy by biochemical assessment at 3 months after treatment
Time Frame
3 months
Title
Number of participants with postoperative hypocortisolism
Description
Number of participants with postoperative hypocortisolism after EUS-RFA will be compared with unilateral adrenalectomy. In patients with an abnormal pre-treatment 1 mg dexamethasone suppression test or a low morning cortisol < 300 nmol/L after RFA or adrenalectomy, individual advise of cortisone acetate replacement therapy will be given and an stimulation adrenocorticotropic hormone (ACTH) test will be performed in the Endocrinology Out-patient clinic ~ 6 weeks of discharge
Time Frame
6 weeks
Title
Change from baseline in health-related quality of life at 1 year
Description
Change in health-related quality of life after treatment compared with pre-treatment, will be measured by the validated RAND-36 Health Survey, and will be compared in the EUS-RFA group and adrenalectomy group. All participants will fill out a RAND-36 form prior to treatment, and repeated 1 year after treatment
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 to 60 years Signed written informed consent PA diagnosis confirmed according to Endocrine Society PA Guideline criteria AVS lateralisation to one adrenal (lateralisation index ≥ 4,0) If CT scan shows an adrenal nodule to the same adrenal as AVS lateralisation result: nodule size < 4 cm and enhancement criteria for adrenal adenoma (native hounsfield units < 10 or relative wash-out > 40% or absolute wash-out > 60%) For EUS-RFA group: AVS lateralisation to the left adrenal only and EUS-guided tissue sampling of detected adrenal tumour for morphologic and functional characterisation confirming benign tumour tissue with aldosterone-producing cells Exclusion Criteria: Age <18 or > 60 years CT scan or histological suspicion of adrenal malignancy Patient refusal to undergo either EUS-RFA or adrenalectomy
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mariann Grytaas, MD phd
Phone
004741545435
Email
marianne.grytaas@helse-bergen.no
First Name & Middle Initial & Last Name or Official Title & Degree
Khanh Cong Do Pham, MD
Email
khanh.cong.do.pham@helse-bergen.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marianne Grytaas, MD phd
Organizational Affiliation
Haukeland University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Haukeland University Hospital
City
Bergen
ZIP/Postal Code
5021
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marianne Grytaas, MD phd
Phone
+4741545435
Email
marianne.grytaas@helse-bergen.no
First Name & Middle Initial & Last Name & Degree
Kristian Løvås, Prof., MD
Email
kristian.lovas@helse-bergen.no

12. IPD Sharing Statement

Learn more about this trial

Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism

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