A Prospective Randomised Trial Comparing Radiofrequency Ablation With Laparoscopic Adrenalectomy as an alternatiVE Treatment for Unilateral Asymmetric Primary Aldosteronism

Study Overview
=================
Brief Summary
-----------------
A prospective randomised trial comparing radiofrequency ablation With laparoscopic Adrenalectomy as an alternatiVE treatment for unilateral asymmetric primary aldosteronism

Detailed Description
-----------------
The primary objective of WAVE is to test the hypothesis that RFA is non-inferior to surgery in the biochemical (and if so, in the clinical) cure of unilateral PA, according to the international consensus PASO criteria. Secondary objectives are to determine whether either intervention is superior to the other in relation to the following outcomes. Where no superiority of either intervention is established, non-inferiority of RFA against LA will be sought. Frequency and severity of adverse events Length of inpatient stay Patient satisfaction Quality of life Return to work An additional secondary objective in the RFA group alone will be anatomical efficacy of ablation.

Official Title
-----------------
A Prospective Randomised Trial Comparing Radiofrequency Ablation With Laparoscopic Adrenalectomy as an alternatiVE Treatment for Unilateral Asymmetric Primary Aldosteronism

Conditions
-----------------
Primary Aldosteronism

Intervention / Treatment
-----------------
* Procedure: ablation of aldosterone secreting adenoma
* Procedure: Unilateral adrenalectomy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age > 18 years Primary aldosteronism according to international guidelines11,14 1. An elevated ARR (according to local reference ranges), and at least one of (when measured off confounding medications): Spontaneous or thiazide-induced hypokalaemia, PAC >550pmol/L and PRA <0.5nmol/L/h or DRC <2.5pg/mL A positive saline infusion test (SIT) Four-hour aldosterone >190pmol/L 3. A positive captopril suppression test (CST), either: Failure to suppress two-hour aldosterone by >30% and persistent suppression of PRA/DRC11, or Two-hour aldosterone > 300 pmol/L14 Unilateral PA, defined by at least one of the following criteria: 1. ACTH-stimulated AVS24 Selectivity index (SI) >3, and Lateralisation index (LI) > 4 2. Non-ACTH-stimulated AVS24 SI > 2, and LI > 3, and Contralateral suppression index (CSI) < 0.5/1 3. Metomidate/CETO PET-CT25 >25% higher PET signal (maximum standardised uptake value) over an adenoma compared to the contralateral adrenal 4. Age <35, unilateral adrenal lesion with normal contralateral gland11 Radiological abnormality ipsilateral to side of lateralisation, which is: 1. Benign: Unenhanced CT attenuation <20HU, or Post-contrast CT absolute washout >60%, or Post-contract CT relative washout >40%, or Signal drop-out on out-of-phase MRI 2. Technically amenable to both RFA and surgery (determined at MDT review) Able and willing to give informed consent Exclusion Criteria: Absolute contraindication to α- or β-adrenoceptor antagonist therapy or CT contrast, or Contraindication or unwillingness for either surgery or RFA, or Inability to withdraw β-adrenoceptor antagonist therapy for 2 weeks, or Unwilling to undergo either LA or RFA, or Unwilling to comply with study visit schedule, or Pregnancy or unwillingness to undertake secure contraception for the study duration (female participants only), or Life-limiting comorbidity (at the discretion of the PI) Clinical and/or biochemical evidence of autonomous cortisol secretion sufficient, in the opinion of the patient's physician, to mandate a unilateral adrenalectomy independent of autonomous aldosterone secretion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: PROBE: Prospective Randomised open blinded end point study.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiofrequency ablation of adrenal aldosterone producing adenoma (s)<br>Ablation of adrenal aldosterone producing adenoma(s) | Procedure: ablation of aldosterone secreting adenoma<br>* Radio frequency ablation to Conn's adenoma(s)<br>|
| Other: Unilateral adrenalectomy for aldosterone producing adenoma(s)<br>Unilateral adrenalectomy for laldosterone producing adenoma(s) | Procedure: Unilateral adrenalectomy<br>* Unilateral adrenalectomy for aldosterone secreting adenoma<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalisation of ARR | Normalisation of aldosterone renin ratio | 12 months | 
| Change in systolic and diastolic blood pressure | Home blood pressure average for systolic and diastolic measurements in mmHg | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | recording of adverse events at study timepoints | 12 months | 
| Safety bloods | Safety bloods including Full blood count Electrolytes and urea Amylase/lipase Liver function test serum metanephrines | 12 months | 
| Patient satisfaction questionnaire | Patient satisfaction following intervention using the Freiuburg questionnaire, patient will score 1 to 6 their satisfaction with treatment, with 1 being excellent and 6 being very poor. | 12 months | 
| Quality of Life Questionnaire | Quality of life questionnaire SF36 short form, patient will complete and a multi - item questionnaire and score how they are feeling, the higher the score, the higher the well being. | 12 months | 
| Return to work | Return to work self reported | 12 months | 
| Anatomical efficacy using CETO PET CT (for radiofrequency ablation arm only | CETO PET CT following radiofrequency ablation for efficacy and change in appearance of aldosterone producing adenoma | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ablation