Endoscopic Ultrasound-guided Radiofrequency Ablation in Primary Aldosteronism

Sponsor

Haukeland University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05368090

Collaborator

(none)

Enrollment

Location

Arms

78.9

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Primary Aldosteronism Aldosterone-Producing Adenoma	Procedure: EUS-RFA of left adrenal gland Procedure: adrenalectomy	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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.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)

Primary Purpose:

Treatment

Official Title:

Endoscopic Ultrasound-guided Radiofrequency Ablation as a Novel Treatment Option Compared With Adrenalectomy in Left-sided Primary Aldosteronism

Actual Study Start Date :

Jun 3, 2022

Anticipated Primary Completion Date :

Dec 31, 2028

Anticipated Study Completion Date :

Dec 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: EUS-RFA of left adrenal gland treatment group 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.	Procedure: EUS-RFA of left adrenal gland 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
Active Comparator: Adrenalectomy control group 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	Procedure: adrenalectomy 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.

Arm

Intervention/Treatment

Experimental: EUS-RFA of left adrenal gland treatment group

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.

Procedure: EUS-RFA of left adrenal gland

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

Active Comparator: Adrenalectomy control group

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

Procedure: adrenalectomy

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.

Outcome Measures

Primary Outcome Measures

Biochemical outcome after EUS-RFA compared with unilateral adrenalectomy [3 months]
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 [1 year]
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 [1 year]
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 [3 months]
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 [3 months]
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 [3 months]
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 [6 weeks]
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 [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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts 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