IS Metomidate PET-CT Superior to Adrenal Venous Sampling in Predicting Outcome From Adrenalectomy in Patients With Primary Hyperaldosteronism

NCT02945904 | Completed DMC

• 1 other identifier: 011149
• Study Type: observational
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose of this clinical trial is to improve prediction of outcomes from surgical intervention in patients with Primary aldosteronism, and evaluate the merits of non-invasive metomidate PET CT versus adrenal vein sampling in the diagnosis of surgically correctable aldosteronism.

Conditions

Primary Aldosteronism; Hyperaldosteronism

Outcome Measures

Primary Outcomes (2)

• Normalisation of aldosterone renin ratio (ARR)

  change in aldosterone- renin ratio for renin activity/renin mass

  Baseline to 6 month Primary endpoint

• Mean home systolic blood pressure

  Changes in average home systolic blood pressures

  Baseline to 6 month primary endpoint

Secondary Outcomes (9)

• Biochemical success using PASO categorical criteria complete, partial or absent

  Baseline to 6 month Primary endpoint

• Clinical success using PASO categorical criteria complete, partial or absent

  Baseline to 6 month Primary endpoint

• Normal range serum potassium levels

  Baseline to 6 month Primary endpoint

• Change in Aldosterone - renin ratio renin activity/renin mass (ARR)

  Baseline to 6 month Primary endpoint

• Change in home systolic and diastolic blood pressure

  Baseline to 6 month Primary endpoint

Interventions

adrenalectomy PROCEDURE

Unilateral adrenalectomy for Conn's adenoma

Eligibility Criteria

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

Study Population

Patients diagnosed with primary aldosteronism

You may qualify if:

• Male or female: Age \>18 yrs.
• Diagnosis of PHA based on current published Endocrine Society consensus guidelines (Funder et al 2016)
• Patients will be enrolled/consented when they have had each of the following:
• At least one paired measurement of plasma renin and aldosterone, measured off spironolactone/eplerenone, showing an elevated ARR. With
• either a plasma aldosterone \>190 pmol/L after saline infusion
• or 'spontaneous hypokalemia + plasma renin below detection levels + plasma aldosterone \> 550 pmol/L)' (as per Endocrine Society guidance, 2016)
• or failure to suppress plasma aldosterone by 30% + persistent PRA suppression after oral administration of captopril (as per Endocrine Society guidance, 2016)
• and a CT or MRI scan of the adrenals with probable or definite adenoma(s) within the last five years
• Patients with elevated ARR can be put forward for consideration by the MDT as exceptional cases in whom spironolactone/eplerenone is not (fully) withdrawn, and/or saline suppression is not performed, IF:
• Plasma Aldosterone \> 450 pmol/L AND plasma renin \<0.5 pmol/ml/hr (\<9 mU/L) if measured on treatment with ACEI (Lisinopril \>=20 mg or equivalent) or ARB (Losartan 100 mg or equivalent); OR
• Age \<40 AND definite adrenal adenoma on CT or MRI Patients whose CT/MRI does not show probable or definite adenoma must also be reviewed by MDT before enrolment/consent
• Any exception to the above diagnostic criteria will be subject to approval by monthly MDT.

You may not qualify if:

• Those patients who indicate that they are unlikely to proceed with surgery will not be recruited, because there will be no outcome change in blood pressure, restoration of normal renin/angiotensin physiology) against which to compare the accuracy of the two Investigations.
• Patients contraindicated for spironolactone or eplerenone therapy.
• Any patients continuing on beta-blockers or direct renin blockers .
• Patients with eGFR \<30 ml/min/ or expected to have a reduction in eGFR\<30ml/min on aldosterone antagonist therapy.
• Pregnant / breastfeeding females unable/unwilling to take secure contraceptive precautions whilst undergoing investigations.
• Patients unwilling/unable to take the dexamethasone required to prepare for a metomidate PET-CT scan.
• Patients unwilling to have both 11- C Metomidate PET CT scan and Adrenal Vein Sampling.
• Any illness, condition or drug regimen that is considered a contraindication by the PI

Sponsors & Collaborators

• Queen Mary University of London: lead
• National Institute for Health Research, United Kingdom: collaborator
• WBIC), Cambridge. University of Cambridge Addenbrookes Hospital, Cambridge CB2 2QQ: collaborator
• Robertson Centre for Biostatistics University of Glasgow Glasgow G12 8QQ: collaborator
• Barts and the London School of Medicine and Dentistry W Smithfield London - City of London EC1A 7BE: collaborator

Study Sites (1)

Queen Mary University of London

City of London, EC1 6BQ, United Kingdom

Location

Related Publications (2)

• Goodchild E, Wu X, Senanayake R, MacFarlane J, Argentesi G, Laycock K, Bashari WA, Cabrera CP, O'Toole SM, Salsbury J, Benu D, Lee YN, Chua ACN, Matson M, Koo B, Parvanta L, Hilliard N, Kosmoliaptsis V, Marker A, Berney DM, Drew K, Tan W, Foo R, Mein CA, Wozniak E, Kearney J, Savage E, Sahdev A, Bird N, Smith G, Hird M, Warnes V, Gillett D, Dawnay A, Adeyeye E, Aigbirhio F, McIntosh A, McConnachie A, Cruickshank JK, Cheow H, Gurnell M, Drake WM, Brown MJ. Molecular Imaging Versus Adrenal Vein Sampling for the Detection of Surgically Curable Primary Aldosteronism : A Prospective Within-Patient Trial. Ann Intern Med. 2025 Mar;178(3):336-347. doi: 10.7326/ANNALS-24-00761. Epub 2025 Mar 4.

  PMID: 40030172 DERIVED

• Wu X, Senanayake R, Goodchild E, Bashari WA, Salsbury J, Cabrera CP, Argentesi G, O'Toole SM, Matson M, Koo B, Parvanta L, Hilliard N, Kosmoliaptsis V, Marker A, Berney DM, Tan W, Foo R, Mein CA, Wozniak E, Savage E, Sahdev A, Bird N, Laycock K, Boros I, Hader S, Warnes V, Gillett D, Dawnay A, Adeyeye E, Prete A, Taylor AE, Arlt W, Bhuva AN, Aigbirhio F, Manisty C, McIntosh A, McConnachie A, Cruickshank JK, Cheow H, Gurnell M, Drake WM, Brown MJ. [11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial. Nat Med. 2023 Jan;29(1):190-202. doi: 10.1038/s41591-022-02114-5. Epub 2023 Jan 16.

  PMID: 36646800 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Following adrenalectomy tissue will be genotyped for somatic mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, CTNNB1 and phenotyping by histological grading, gene expression and immunohistochemistry.

MeSH Terms

Conditions

Hyperaldosteronism

Interventions

Adrenalectomy

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Endocrine Surgical Procedures; Surgical Procedures, Operative

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 5, 2016
• First Posted: October 26, 2016
• Study Start: December 1, 2016
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: March 10, 2025

Record last verified: 2025-03

Locations

GB (1)