Unilateral Primary Aldosteronism, Mineralocorticoid Antagonists Versus Surgical Treatment

NCT05797558 | Recruiting

• 2 other identifiers: ALFGBG-978940DNR 2020-02008
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

This is a prospective randomized controlled trial where quality of life and the effectiveness of treatment will be evaluated in 80 patients with confirmed unilateral primary aldosteronism ,randomly assigned to be either treated surgically with unilateral adrenalectomy or to receive medical treatment with eplerenone.

Conditions

Primary Hyperaldosteronism Due to Adrenal Adenoma

Keywords

hyperaldosteronism; primary aldosteronism; lateralized aldosteronism; unilateral aldosteronism; eplerenone; spironolactone; randomized trial; quality of life; PASO outcomes

Outcome Measures

Primary Outcomes (4)

• Quality of Life (QoL) evaluated with EuroQol-5D at 12 months

  Improvement in quality of life in surgically and medically treated patients 1 year after treatment of unilateral primary aldosteronism evaluated with EuroQol-5D (EQ-5D-5LTM)

  1 year

• Quality of Life (QoL) evaluated with RAND SF-36 at 12 months

  Improvement in quality of life in surgically and medically treated patients 1 year after treatment of unilateral primary aldosteronism evaluated with RAND SF-36.

  1 year

• Quality of Life (QoL) evaluated with EuroQol-5D at 24 months

  Improvement in quality of life 2 years after treatment of unilateral primary aldosteronism evaluated with EuroQol-5D (EQ-5D-5LTM)

  2 years

• Quality of Life (QoL) evaluated with RAND SF-36 at 24 months

  Improvement in quality of life 2 years after treatment of unilateral primary aldosteronism evaluated with RAND SF-36.

  2 years

Secondary Outcomes (7)

• Clinical outcome based on the Primary Aldosteronism Surgical Outcome (PASO) Criteria

  1 year

• Biochemical outcome based on the Primary Aldosteronism Surgical Outcome (PASO) Criteria

  1 year

• Left ventricular mass

  1 year

• Left ventricular mass

  2 year

• Glomerular filtration rate (GFR) as a surrogate endpoint of renal function at 12 months

  1 year

Study Arms (2)

Surgically Treated Primary Aldosteronism

ACTIVE COMPARATOR

Standard therapy

Procedure: Unilateral adrenalectomy

Medically Treated Unilateral Primary Aldosteronism

ACTIVE COMPARATOR

Open label eplerenone treatment

Drug: Medical treatment (eplerenone)

Interventions

Unilateral adrenalectomy PROCEDURE

Minimally invasive surgery is performed via the lateral transperitoneal approach or the posterior retroperitoneal approach, with or without robotic assistance, according to the surgeon's preference.

Also known as: Surgery

Surgically Treated Primary Aldosteronism

Medical treatment (eplerenone) DRUG

The initial dose of eplerenone is 25 mg twice daily. The dose will be increased by 50 mg every fourth week until systolic blood pressure of 140 mmHg and diastolic blood pressure of 90 mmHg or lower has been reached and biochemical control (plasma renin above the middle of the reference range, i.e \> \~20 mIU/L) is attained and/or hyperkalemia develops. The maximal dose of eplerenone is 300 mg twice daily.

Also known as: Mineralocorticoid receptor antagonists

Medically Treated Unilateral Primary Aldosteronism

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with confirmed unilateral PA
• Age 18-70 years
• Candidate for surgical treatment
• No contraindications for minimally invasive surgery or treatment with MRA
• Understands oral and written information and provides oral and written informed consent.

You may not qualify if:

• Unwilling or unable to undergo surgery
• Unwilling to accept medical treatment for 12 months and not receiving standard treatment (surgery)
• Impaired renal function with eGFR \<45 ml/min/1,73m2
• P-cortisol \>138 nmol/L following 1-mg overnight dexamethasone suppression test.

Sponsors & Collaborators

• Göteborg University: lead
• Karolinska Institutet: collaborator
• Umeå University: collaborator

Study Sites (3)

University of Gothenburg

Gothenburg, 41345, Sweden

RECRUITING

Karolinska University Hospital, Stockholm, Sweden.

Stockholm, Sweden

NOT YET RECRUITING

Umeå University, Umeå, Sweden.

Umeå, Sweden

NOT YET RECRUITING

Related Publications (11)

• Young WF Jr. Diagnosis and treatment of primary aldosteronism: practical clinical perspectives. J Intern Med. 2019 Feb;285(2):126-148. doi: 10.1111/joim.12831. Epub 2018 Sep 25.

  PMID: 30255616 BACKGROUND

• Monticone S, Burrello J, Tizzani D, Bertello C, Viola A, Buffolo F, Gabetti L, Mengozzi G, Williams TA, Rabbia F, Veglio F, Mulatero P. Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice. J Am Coll Cardiol. 2017 Apr 11;69(14):1811-1820. doi: 10.1016/j.jacc.2017.01.052.

  PMID: 28385310 BACKGROUND

• Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018 Jan;6(1):41-50. doi: 10.1016/S2213-8587(17)30319-4. Epub 2017 Nov 9.

  PMID: 29129575 BACKGROUND

• Muth A, Ragnarsson O, Johannsson G, Wangberg B. Systematic review of surgery and outcomes in patients with primary aldosteronism. Br J Surg. 2015 Mar;102(4):307-17. doi: 10.1002/bjs.9744. Epub 2015 Jan 20.

  PMID: 25605481 BACKGROUND

• Huang WC, Chen YY, Lin YH, Chueh JS. Composite Cardiovascular Outcomes in Patients With Primary Aldosteronism Undergoing Medical Versus Surgical Treatment: A Meta-Analysis. Front Endocrinol (Lausanne). 2021 May 17;12:644260. doi: 10.3389/fendo.2021.644260. eCollection 2021.

  PMID: 34079522 BACKGROUND

• Ahmed AH, Gordon RD, Sukor N, Pimenta E, Stowasser M. Quality of life in patients with bilateral primary aldosteronism before and during treatment with spironolactone and/or amiloride, including a comparison with our previously published results in those with unilateral disease treated surgically. J Clin Endocrinol Metab. 2011 Sep;96(9):2904-11. doi: 10.1210/jc.2011-0138. Epub 2011 Jul 21.

  PMID: 21778218 BACKGROUND

• Velema M, Dekkers T, Hermus A, Timmers H, Lenders J, Groenewoud H, Schultze Kool L, Langenhuijsen J, Prejbisz A, van der Wilt GJ, Deinum J; SPARTACUS investigators. Quality of Life in Primary Aldosteronism: A Comparative Effectiveness Study of Adrenalectomy and Medical Treatment. J Clin Endocrinol Metab. 2018 Jan 1;103(1):16-24. doi: 10.1210/jc.2017-01442.

  PMID: 29099925 BACKGROUND

• Hundemer GL, Curhan GC, Yozamp N, Wang M, Vaidya A. Cardiometabolic outcomes and mortality in medically treated primary aldosteronism: a retrospective cohort study. Lancet Diabetes Endocrinol. 2018 Jan;6(1):51-59. doi: 10.1016/S2213-8587(17)30367-4. Epub 2017 Nov 9.

  PMID: 29129576 BACKGROUND

• Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2.

  PMID: 26934393 BACKGROUND

• Zhou Y, Wang D, Jiang L, Ran F, Chen S, Zhou P, Wang P. Diagnostic accuracy of adrenal imaging for subtype diagnosis in primary aldosteronism: systematic review and meta-analysis. BMJ Open. 2020 Dec 31;10(12):e038489. doi: 10.1136/bmjopen-2020-038489.

  PMID: 33384386 BACKGROUND

• Schirpenbach C, Segmiller F, Diederich S, Hahner S, Lorenz R, Rump LC, Seufert J, Quinkler M, Bidlingmaier M, Beuschlein F, Endres S, Reincke M. The diagnosis and treatment of primary hyperaldosteronism in Germany: results on 555 patients from the German Conn Registry. Dtsch Arztebl Int. 2009 May;106(18):305-11. doi: 10.3238/arztebl.2009.0305. Epub 2009 May 1.

  PMID: 19547646 BACKGROUND

MeSH Terms

Conditions

Hyperaldosteronism

Interventions

Surgical Procedures, Operative; Eplerenone; Mineralocorticoid Receptor Antagonists

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Diuretics, Potassium Sparing; Diuretics; Natriuretic Agents

Study Officials

• Oskar Ragnarsson, MD

  Institute of Medicine, Sahlgrenska Academy, University of Gothenburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Oskar Ragnarsson, MD

CONTACT

00460313421000; oskar.ragnarsson@medic.gu.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PHD, Associate Professor

Model Details: Unblinded, prospective, multi-center,randomized, controlled trial.

Study Record Dates

• First Submitted: February 5, 2023
• First Posted: April 4, 2023
• Study Start: April 28, 2023
• Primary Completion (Estimated): May 28, 2028
• Study Completion (Estimated): May 28, 2028
• Last Updated: April 6, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The investigators expect to start patient recruitment in February 2023. With an annual AVS rate of 50-70 patients with PA at Gothenburg University Hospital, with an AVS success rate of 97% (13), where approximately 50% are diagnosed with unilateral PA, and a sample size of 80, the estimated accrual time is set to 4 years. To increase the external validity of the study, and to speed up the recruitment period, other centres of excellence for patients with PA will be offered to participate in the study.
• Access Criteria: All data will be available for other researcher upon request

Locations

SE (3)