Prospective Evaluation of Confirmatory Testing for Primary Aldosteronism

NCT04422756 | Completed

• 1 other identifier: REB16-2322
• Study Type: observational
• Target: 183
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to evaluate the performance characteristics of the seated saline infusion test and the ultra low-dose ACTH stimulation test for the diagnosis of primary aldosteronism.

Conditions

Primary Aldosteronism

Outcome Measures

Primary Outcomes (1)

• Diagnostic accuracy of confirmatory testing (seated saline infusion test and the ultra low-dose ACTH stimulation test)

  Measures of diagnostic accuracy, as summarized by receiver operating characteristic curve analyses.

  The total study timeline will occur over 66 months.

Secondary Outcomes (2)

• The optimal cutoff value for confirmatory testing using clinically-important thresholds

  The total study timeline will occur over 66 months.

• The optimal cutoff value for confirmatory testing using clinically-important thresholds

  The total study timeline will occur over 66 months.

Interventions

Seated intravenous saline infusion test DIAGNOSTIC_TEST

The test will be conducted by infusing two litres of normal saline intravenously over 4 hours with the patient seated.Blood collection (for aldosterone, cortisol, renin, and electrolytes) will be performed at baseline and after completion of the infusion. Following infusion, plasma aldosterone levels \<140 pmol/L will be considered as "negative," levels \>280 pmol/L as "positive," and levels in between classified as indeterminate.

Ultra low-dose ACTH stimulation test DIAGNOSTIC_TEST

The test will be performed by injecting 0.03 mcg of ACTH intravenously. Blood collection (for aldosterone, cortisol, and renin) will be performed at baseline and after 15 minutes. We expect a "positive" response to correspond with a plasma aldosterone \>2200 pmol/L and ARR \>220 pmol/L/mIU/L following stimulation.

Eligibility Criteria

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

Study Population

Hypertension individuals suspected of having primary aldosteronism.

You may qualify if:

• Individuals with hypertension
• Individuals with an elevated screening adrenal renin ration (ARR)
• Individuals with high probability features of primary aldosteronism (e.g., resistant hypertension, spontaneous or diuretic-induced hypokalemia, and/or an adrenal nodule) with clinical indications for adrenal vein sampling and surgery (if appropriate).

You may not qualify if:

• Individuals with chronic kidney disease (estimated glomerular filtration rate \<40 mL/min/1.73m2),
• Individuals with a history of heart failure, chronic edema, uncontrolled severe hypertension (systolic blood pressure \>180 and/or diastolic blood pressure \>110 mmHg), untreated hypokalemia, cortisol-secreting adrenal adenoma, and/or pheochromocytoma
• Individual who previously received confirmatory testing.

Sponsors & Collaborators

• University of Calgary: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Hypertension Canada: collaborator

Study Sites (1)

University of Calgary

Calgary, Alberta, Canada

Location

Related Publications (5)

• Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Tobe SW, Ruzicka M, Burns KD, Vallee M, Prasad GV, Lebel M, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Penner SB, Burgess E, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NR, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Trudeau L, Petrella RJ, Hiremath S, Drouin D, Lavoie KL, Hamet P, Fodor G, Gregoire JC, Lewanczuk R, Dresser GK, Sharma M, Reid D, Lear SA, Moullec G, Gupta M, Magee LA, Logan AG, Harris KC, Dionne J, Fournier A, Benoit G, Feber J, Poirier L, Padwal RS, Rabi DM; CHEP Guidelines Task Force. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol. 2016 May;32(5):569-88. doi: 10.1016/j.cjca.2016.02.066. Epub 2016 Mar 10.

  PMID: 27118291 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

• Mulatero P, Milan A, Fallo F, Regolisti G, Pizzolo F, Fardella C, Mosso L, Marafetti L, Veglio F, Maccario M. Comparison of confirmatory tests for the diagnosis of primary aldosteronism. J Clin Endocrinol Metab. 2006 Jul;91(7):2618-23. doi: 10.1210/jc.2006-0078. Epub 2006 May 2.

  PMID: 16670162 BACKGROUND

• Leung AA, Padwal RS, Hundemer GL, Venos E, Campbell DJT, Holmes DT, Orton DJ, So CB, Przybojewski SJ, Caughlin CE, Pasieka JL, Rabi DM, Kline GA. Seated Saline Suppression Test for Lateralizing Primary Aldosteronism. Hypertension. 2026 Jan 26. doi: 10.1161/HYPERTENSIONAHA.125.26008. Online ahead of print.

  PMID: 41582811 DERIVED

• Leung AA, Padwal RS, Hundemer GL, Venos E, Campbell DJT, Holmes DT, Orton DJ, So CB, Przybojewski SJ, Caughlin CE, Pasieka JL, Rabi DM, Kline GA. Confirmatory Testing for Primary Aldosteronism : A Study of Diagnostic Test Accuracy. Ann Intern Med. 2025 Jul;178(7):948-956. doi: 10.7326/ANNALS-24-03153. Epub 2025 May 6.

  PMID: 40324193 DERIVED

MeSH Terms

Conditions

Hyperaldosteronism

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Study Officials

• Alexander Leung, Asst. Prof

  University of Calgary

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 27, 2020
• First Posted: June 9, 2020
• Study Start: January 15, 2017
• Primary Completion: August 31, 2024
• Study Completion: August 31, 2024
• Last Updated: March 30, 2025

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)