Condition category
Circulatory System
Date applied
03/01/2018
Date assigned
12/01/2018
Last edited
12/01/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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 December 2020

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

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

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Jackie Salsbury

ORCID ID

Contact details

The Barts Heart Centre
William Harvey Research Institute
Queen Mary University of London
Charterhouse Square
London
EC1M 6B
United Kingdom
+44 (0)207 882 3991
j.salsbury@qmul.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

34735

Study information

Scientific title

Feasibility study of RadioFrequency endoscopic ABlation, with ULtrasound guidance, as a non-surgical, Adrenal Sparing treatment for aldosterone-producing adenomas

Acronym

FABULAS

Study hypothesis

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

London - Bloomsbury Research Ethics Committee, 17/10/2017, ref: 17/LO/0948, IRAS project ID: 222446

Study design

Non-randomised; Interventional; Design type: Treatment, Management of Care

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

Specialty: Cardiovascular disease, Primary sub-specialty: Cardiovascular Prevention; UKCRC code/ Disease: Cardiovascular/ Hypertensive diseases

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

Phase

Drug names

Primary outcome measures

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

Secondary outcome measures

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

Overall trial start date

01/04/2016

Overall trial end date

01/12/2020

Reason abandoned

Eligibility

Participant 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.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 30; UK Sample Size: 30

Participant 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

Recruitment start date

20/01/2018

Recruitment end date

20/11/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St Bartholomew's Hospital
West Smithfield
London
EC1 A7BE
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Portfolio Coordinator JRO
UCL Gower Street
London
WC1E 6BT
United Kingdom
+44 (0)7918 030401
randd@uclh.nhs.uk

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

British Heart Foundation (BHF); Grant Codes: PG/16/40/32137

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Following statistical analysis the trialists aim to present results at hypertension and endocrine symposiums/conferences with publications in lead cardiovascular and endocrine journals.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

30/12/2021

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes