The primary objective of WAVE is to test the hypothesis that thermal ablation (microwave or 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 thermal ablation against adrenalectomy will be sought.
* Frequency and severity of adverse events * Length of inpatient stay * Patient satisfaction * Quality of life * Return to activities of daily living
An additional secondary objective in the thermal ablation group alone will be anatomical efficacy of ablation.
Age > 18 years
Primary aldosteronism diagnosed according to international guidelines
Unilateral disease by AVS or PET-CT criteria
Ipsilateral radiological abnormality with benign imaging characteristics and technically amenable to both thermal ablation and surgery
Absolute contraindication to α- or β-adrenoceptor antagonist therapy or CT contrast
Contraindication or unwillingness for either surgery or thermal ablation
Inability to withdraw β-adrenoceptor antagonist therapy for 2 weeks
Unwilling to undergo either LA or thermal ablation
Single group
Thermal ablation of aldosterone producing adenoma.
Procedure/SurgeryOn the left side, Radiofrequency ablation of aldosterone producing adenoma(s) will be undertaken via the stomach (endoscopically), under transgastric ultrasound guidance. On the right side, either Radiofrequency or Microwave Ablation of aldosterone producing adenoma(s) will be performed via a percutaneous approach, under CT guidance.
Unilateral adrenalectomy
Procedure/SurgeryUnilateral total adrenalectomy for aldosterone producing adenoma. This will be laparoscopic in the vast majority of patients, with open conversion if surgically indicated (unlikely in \>1-2 patients)
Complete biochemical cure of PA
Complete biochemical cure of PA, defined (whilst off medications that might alter serum potassium or the RAS) by both: 1. Normalisation of serum potassium, and 2. Normalisation of ARR, or 3. Elevated ARR and i. Baseline PAC \<190pmol/L, or ii. Normal confirmatory test (as defined in the inclusion criteria)
Complete clinical cure of PA
Complete clinical cure of PA, defined as normotension without antihypertensive medication These criteria have been defined in the international consensus PASO statement8, which has become the established yardstick by which PA cure is judged. In this, normotension is defined, in accordance with the European Society of Hypertension guidelines22, as \<140/80 in the office, \<135/85 at home or daytime ambulatory monitoring and \<130/80 for 24h ambulatory blood pressure monitoring (24hABPM).
Adverse events
* Will be directly sought at each study visit through history and physical examination where appropriate * Subjects will be encouraged to report between study visits and will have a mechanism to do so * Will be classified by system, seriousness, causal relationship and expectedness according to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE)
Anaemia (FBC, requirement for blood transfusion)
Blood test
Renal dysfunction and electrolyte abnormalities (U&Es)
Blood test
Liver dysfunction (LFTs)
Blood test
Hierarchical analysis testing
Hierarchical analysis testing will be applied to sequential testing of the following hypotheses. Each positive outcome permits the next limb to be tested as a co-primary hypothesis. A negative outcome converts subsequent limbs to secondary hypotheses. \[i\] Complete biochemical cure for left ablation vs left surgery (positive if non-inferiority (NI) margin \<45%) \[ii\] Complete biochemical cure for all ablation vs all surgery (positive if NI margin \<45%) \[iii\] Complete clinical cure for all ablation vs all surgery (positive if NI margin \<33%) The first limb of the hierarchy will be tested if sufficient patients have been recruited on the left, anticipated to be 3 times as many as on the right.
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