Feasibility study of radiofrequency endoscopic ablation, with ultrasound guidance, as a non-surgical, adrenal sparing treatment for aldosterone-producing adenomas

ISRCTN	ISRCTN86062633
DOI	https://doi.org/10.1186/ISRCTN86062633
ClinicalTrials.gov (NCT)	NCT03405025
Clinical Trials Information System (CTIS)	Nil known
Protocol serial number	34735
Sponsor	University College London
Funder	British Heart Foundation (BHF); Grant Codes: PG/16/40/32137

Submission date: 03/01/2018
Registration date: 12/01/2018
Last edited: 23/06/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
High blood pressure (hypertension) causes strokes and heart attacks. While most patients need long-term treatment with pills, some have a cause which can be removed, curing the hypertension. The commonest curable cause is a benign nodule (adenoma) in one of the hormone glands, the adrenals, causing a condition called primary hyperaldosteronism. About one in 20 patients have such a nodule, but difficulties with diagnosis, and reluctance to undergo surgery for a benign condition, limit the number having adrenal gland surgery to fewer than 300 per year in the UK. A potential, and exciting, solution to this dilemma is to use a momentary electric current to cauterise the nodule (radiofrequency ablation), without affecting the rest of the adrenal gland, and avoiding the need for surgery. Nodules in the left adrenal gland are easily reached under mild sedation using a similar procedure as is standard for investigating stomach ulcers (endoscopy). The aim of this study is to show that this approach (called endoscopic ultrasound guided radiofrequency ablation) is very safe, and to provide initial evidence that the hormone abnormality is cured.

Who can participate?
Patients aged 18 and over with primary hyperaldosteronism

What does the study involve?
A probe is placed under ultrasound guidance by an experienced endoscopist into the identified aldosterone-producing adenoma of the affected left adrenal gland. Ablation is then achieved using electrical energy for a total of up to 25 minutes (10x90 second applications with 60 seconds rest between applications) to remove the aldosterone-producing adenoma. All patients following treatment attend follow up clinic visits as per the study schedule. The total duration for treatment to follow up is 6 months.

What are the possible benefits and risks of participating?
The study is expected to demonstrate that the treatment is safe and offers similar cure rates to surgical removal of the whole adrenal gland, which is the usual treatment. If ablation is effective, its benefit is transformational, allowing patients to have the benefits of surgery without the side effects, and opening up a potential cure for hypertension to a much larger number of patients. Although the endoscopic route is likely to be lower risk there needs to be a formal assessment of its safety and potential effectiveness for controlling high blood pressure.

Where is the study run from?
St Bartholomew's Hospital (UK)

When is the study starting and how long is it expected to run for?
April 2016 to September 2022

Who is funding the study?
British Heart Foundation (BHF) (UK)

Who is the main contact?
Jackie Salsbury
j.salsbury@qmul.ac.uk

Contact information

Mrs Jackie Salsbury
Scientific

The Barts Heart Centre
William Harvey Research Institute
Queen Mary University of London
Charterhouse Square
London
EC1M 6B
United Kingdom

Phone	+44 (0)207 882 3991
Email	j.salsbury@qmul.ac.uk

Study information

Primary study design	Interventional
Study design	Non-randomised; Interventional; Design type: Treatment, Management of Care
Secondary study design	Non randomised study
Study type	Participant information sheet
Scientific title	Feasibility study of RadioFrequency endoscopic ABlation, with ULtrasound guidance, as a non-surgical, Adrenal Sparing treatment for aldosterone-producing adenomas
Study acronym	FABULAS
Study objectives	High blood pressure (hypertension) causes strokes and heart attacks. While most patients need long-term treatment with pills, some have a cause which can be removed, curing the hypertension. The commonest curable cause is a benign nodule in one of the hormone glands, the adrenals. About one in 20 patients have such a nodule, but difficulties with diagnosis, and reluctance to proceed to surgery for a begnin condition, limit the number having adrenal gland surgery to fewer than 300 per year in the UK. A potential, and exciting, solution to this dilemma is to use a momentary electric current to cauterise the nodule (radiofrequency ablation), without affecting the rest of the adrenal gland, and avoiding the need for surgery. Nodules in the left adrenal gland are easily reached under mild sedation using a similar procedure as is standard for investigating stomach ulcers (endoscopy). This study is designed to show that this approach (endoscopic ultrasound guided radiofrequency ablation) is very safe, and to provide initial evidence that the hormone abnormality is cured.
Ethics approval(s)	London - Bloomsbury Research Ethics Committee, 17/10/2017, ref: 17/LO/0948, IRAS project ID: 222446
Health condition(s) or problem(s) studied	Aldosterone producing adenoma
Intervention	Treatment is via a single monopolar probe placed under EUS guidance by an experienced endoscopist into the identified aldosterone-producing adenoma of the affected left adrenal gland. Ablation is then achieved using an RFA generator to deliver sequential doses of electrical energy at 10W for a total of up to 25 minutes (10x90 second applications with 60 seconds rest between applications) to ablate the aldosterone producing adenoma. All patients following treatment will undergo surveillance with follow up clinic visits as per study schedule. The total duration for treatment to follow up is 6 months.
Intervention type	Procedure/Surgery
Primary outcome measure(s)	There will be a hierarchical co-primary endpoint. The first co-primary is whether the recorded patient safety outcome data establishes that perforation, haemorrhage infarction of major organs did not occur. This will be assessed at 48 hours. The second co-primary endpoint is efficacy, assessed biochemically at 3 months post ablation. This will be achieved by: 1. Accurate adverse event reporting 2. Clinical assessment by history and examination looking for features of blood loss, perforation, or inflammation/infarction of peri-adrenal tissues 3. Blood tests for Hb, WBC, Renal function, amylase, liver function Tests, C Reactive Protein. urinalysis for blood and protein
Key secondary outcome measure(s)	The difference from baseline measurements at 3 and 6 months following ablation for biochemical and radiological parameters as follows: 1. Plasma electrolytes 2. Aldosterone and renin ratio at 3 and 6 months 3. 3 month PET CT will be performed post ablation for radiological disappearance, diameter size and SUV measurements 4. The reduced use/or no longer taking supplementary potassium 5. Home BP will be measured 3 reading twice a day for 4 days preceding clinic visit 6. Assessment of cure will be performed at the site not involved in patient care, and subject to ratification by the safety committee, who are not involved in the study 7. Reduction in/or no longer taking antihypertensive medication 8. No/or reduced doses of potassium supplementation
Completion date	30/09/2022

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	30
Key inclusion criteria	1. Patients aged 18 and above 2. Diagnosis of primary hyperaldosteronism (PHA) based on published Endocrine Society guidelines 3. Positive serum aldosterone renin ratio (ARR) with another local diagnostic confirmatory test (MRI or CT imaging) There are 3 inclusion subset groups: Group 1: 1. Left-sided APA proven on either AVS or PET CT 2. Patients wishing to take fewer drugs for their hypertension 3. Patients not usually referred for surgery because the benefit: risk is considered too low 4. Patients aged ≥60 whose BP is at or near target (BP140/90 for most patient groups, BP 130/80 if co-morbidities listed in Hypertension guidelines) on treatment with four or more drugs 5. Patients with identified macroadenomas (APAs >= 1 cm in diameter), who have at least 1 cm of peri-adrenal fat on axial and coronal projections Group 2: 1. Patients aged 18 years and above with diagnosis of PA and either 2. A definite unilateral left APA, but the patient does not want surgery 3. Probable but not unequivocal evidence of a unilateral left adrenal APA Group 3: Patients over 18 years of age meeting criteria for surgery, but consent to undergo endoscopic ablation instead.
Key exclusion criteria	1. Inability to give informed consent 2. Any patients continuing on beta blockers/direct renin blockers 3. Pregnant women or those unable or unwilling to take secure contraceptive precautions 4. Any illness, condition or drug regimen considered a contraindication by the PI/CI
Date of first enrolment	20/01/2018
Date of final enrolment	20/11/2020

Locations

Countries of recruitment

United Kingdom

Study participating centre

St Bartholomew's Hospital

West Smithfield
London
EC1 A7BE
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
IPD sharing plan	The data sharing plans for the current study are unknown and will be made available at a later date.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

23/06/2022: The overall trial end date has been changed from 01/12/2020 to 30/09/2022 and the plain English summary has been updated accordingly.
21/06/2019: Added Clinicaltrials.gov number
29/03/2019: The condition has been changed from "Specialty: Cardiovascular disease, Primary sub-specialty: Cardiovascular Prevention; UKCRC code/ Disease: Cardiovascular/ Hypertensive diseases" to "Aldosterone producing adenoma" following a request from the NIHR.