Randomised Trial Comparing Thermal Ablation With Adrenalectomy in the Treatment of Unilateral Asymmetric PA

NCT05405101 | Recruiting DMC

• 1 other identifier: 304174
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Primary Aldosteronism

Keywords

Thermal; Ablation; Laparoscopic; Adrenalectomy

Outcome Measures

Primary Outcomes (2)

• 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)

  6 months post intervention

• 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).

  6 months post intervention

Secondary Outcomes (11)

• Adverse events

  Reported throughout the study period. Approximately 2 years

• Anaemia (FBC, requirement for blood transfusion)

  6, 12, 24 and 36 months post intervention

• Renal dysfunction and electrolyte abnormalities (U&Es)

  6, 12, 24 and 36 months post intervention

• Liver dysfunction (LFTs)

  6, 12, 24 and 36 months post intervention

• Pancreatitis (lipase/amylase)

  6, 12, 24 and 36 months post intervention

Other Outcomes (1)

• Hierarchical analysis testing

  6 months post intervention

Study Arms (2)

Thermal ablation of adrenal aldosterone producing adenoma (s)

EXPERIMENTAL

For patients randomized to ablation, thermal ablation (either microwave or radiofrequency ablation) will be deployed to treat the adrenal aldosterone producing adenoma(s)

Procedure: Thermal ablation of aldosterone producing adenoma.

Unilateral adrenalectomy for aldosterone producing adenoma (s)

OTHER

For patients randomized to surgery, unilateral adrenalectomy will be performed to remove aldosterone producing adenoma(s)

Procedure: Unilateral adrenalectomy

Interventions

Thermal ablation of aldosterone producing adenoma. PROCEDURE

On 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.

Thermal ablation of adrenal aldosterone producing adenoma (s)

Unilateral adrenalectomy PROCEDURE

Unilateral 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)

Also known as: Laparoscopic adrenalectomy

Unilateral adrenalectomy for aldosterone producing adenoma (s)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Able and willing to give informed consent
• Randomisation approved by MDT

You may not qualify if:

• 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
• Unwilling to comply with study visit schedule
• Pregnancy or unwillingness to undertake secure contraception for the study duration (female participants only)
• 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

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (6)

Cambridge University Hospitals NHS Foundation Trust

Cambridge, SMLG, CB2 0QQ, United Kingdom

RECRUITING

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

RECRUITING

University College London Hospital NHS Foundation Trust

London, NW1 2PG, United Kingdom

RECRUITING

Guy's and St Thomas' NHS Foundation Trust

London, SE1 9RT, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

RECRUITING

Sheffield Teaching Hospitals NHS Foundation Trust

Sheffield, S10 2JF, United Kingdom

RECRUITING

Related Publications (1)

• Laycock K, Kearney J, Lee YN, Macfarlane J, Goodchild E, Ng E, Pineau Mitchell A, Wu X, Htut Z, Goodchild G, Lowe D, Hilliard N, Godfrey E, Qazi N, Bastos J, Chua A, Mahroof R, Palma A, Khatun A, Varsani C, Benu D, Pereira SP, Krishnamurthy M, Cheow H, Chung TT, Carroll P, O'Toole S, Wernig F, Gurnell M, Brown M, Drake WM. Prospective randomised trial comparing thermal ablation With laparoscopic Adrenalectomy as an alternatiVE treatment for unilateral asymmetric primary aldosteronism: a protocol for the WAVE trial. BMJ Open. 2026 Mar 26;16(3):e111798. doi: 10.1136/bmjopen-2025-111798.

  PMID: 41887640 DERIVED

MeSH Terms

Conditions

Hyperaldosteronism

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Morris Brown

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Aklima Khatun

CONTACT

0203 765 8577; aklima.khatun4@nhs.net

Tumi Kaminsas

CONTACT

0207 882 5994; research.governance@qmul.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: PROBE (Prospective, Randomised, Open-label with Blind Endpoint) multi-centre comparison of thermal ablation with laparoscopic adrenalectomy in the treatment of unilateral asymmetric primary aldosteronism.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: PROBE: Prospective Randomised open blinded end point study. Patients are randomized using a minimization program. 2:3 Surgery: Ablation

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: June 6, 2022
• Study Start: September 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

GB (6)