Primary AldosteronismNCT04422756
Prospective Evaluation of Confirmatory Testing for Primary Aldosteronism
An observational study of Primary Aldosteronism, run by University of Calgary at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Aldosteronism
- What is being tested?
- Seated intravenous saline infusion test and Ultra low-dose ACTH stimulation test
- Type of treatment
- Injection or infusion
- How many people
- 183 participants
- Where
- 1 siteCanada
- Study dates
- 15 Jan 2017to 31 Aug 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Hypertension individuals suspected of having primary aldosteronism.
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
This is a prospective study (with a target recruitment of 200 participants) designed 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, using disease-specific treatment response as a reference gold standard. Subjects consenting to study participation will undergo a standardized seated saline infusion test, followed by an ultra low-dose ACTH stimulation test. All participants also receive adrenal vein sampling. Individuals who have unilateral disease and desire surgery will receive adrenalectomy (as part of routine care) and the remaining subjects will receive medical treatment with a mineralocorticoid receptor antagonist. Response to targeted treatment will be considered the reference gold standard for the establishing the diagnosis of primary aldosteronism.
- Conditions
- Primary Aldosteronism
- Being tested
- Seated intravenous saline infusion test, Ultra low-dose ACTH stimulation test
- Medical subject headings
- Hyperaldosteronism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Seated intravenous saline infusion testDiagnostic 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 testDiagnostic 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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The total study timeline will occur over 66 months.
Secondary outcomes (2)
The optimal cutoff value for confirmatory testing using clinically-important thresholds
Plasma aldosterone
Measured: The total study timeline will occur over 66 months.
The optimal cutoff value for confirmatory testing using clinically-important thresholds
Aldosterone-to-renin ratio
Measured: The total study timeline will occur over 66 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start15 Jan 2017
- Primary completion31 Aug 2024
- Study completion31 Aug 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Primary AldosteronismStudies of the same condition, open and under way.
- More trials run by University of CalgaryThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Calgary
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Hypertension Canada
- Responsible party
- Sponsor
- Investigators
- Alexander Leung, Asst. Prof, Principal investigator, University of Calgary
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04422756
- Sponsor's protocol ID
- REB16-2322
- Status last verified
- Jul 2024
- First submitted
- 27 May 2020
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27118291Funder 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.
PubMed 26934393Mulatero 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.
PubMed 16670162Leung 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 May;83(5):e26008. doi: 10.1161/HYPERTENSIONAHA.125.26008. Epub 2026 Jan 26.
PubMed 41582811Leung 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.
PubMed 40324193
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Confirmatory Testing for Primary Aldosteronism
- ClinicalTrials.gov ID
- NCT04422756
- Acronym / sponsor ID
- REB16-2322
- Conditions
- Primary Aldosteronism
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- University of CalgaryUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), Hypertension Canada
- Study start
- 15 Jan 2017 (actual)
- Primary completion
- 31 Aug 2024 (actual)
- Study completion
- 31 Aug 2024 (actual)
- First posted
- 9 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is a prospective study (with a target recruitment of 200 participants) designed 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, using disease-specific treatment response as a reference gold standard. Subjects consenting to study participation will undergo a standardized seated saline infusion test, followed by an ultra low-dose ACTH stimulation test. All participants also receive adrenal vein sampling. Individuals who have unilateral disease and desire surgery will receive adrenalectomy (as part of routine care) and the remaining subjects will receive medical treatment with a mineralocorticoid receptor antagonist. Response to targeted treatment will be considered the reference gold standard for the establishing the diagnosis of primary aldosteronism.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Hypertension individuals suspected of having primary aldosteronism.
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (3 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Seated intravenous saline infusion testThe 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. | Diagnostic test | – |
| Ultra low-dose ACTH stimulation testThe 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. | Diagnostic test | – |
Primary outcome
Diagnostic accuracy of confirmatory testing (seated saline infusion test and the ultra low-dose ACTH stimulation test)
Time frame: The total study timeline will occur over 66 months.
Measures of diagnostic accuracy, as summarized by receiver operating characteristic curve analyses.
2 secondary outcomes
The optimal cutoff value for confirmatory testing using clinically-important thresholds
Time frame: The total study timeline will occur over 66 months.
The optimal cutoff value for confirmatory testing using clinically-important thresholds
Time frame: The total study timeline will occur over 66 months.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Background: PubMed 27118291Leung 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.
- Background: PubMed 26934393Funder 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.
- Background: PubMed 16670162Mulatero 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.
- Derived from this study: PubMed 41582811Leung 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 May;83(5):e26008. doi: 10.1161/HYPERTENSIONAHA.125.26008. Epub 2026 Jan 26.
- Derived from this study: PubMed 40324193Leung 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alexander Leung, Asst. Prof principal investigator
University of Calgary
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Primary Aldosteronism, run by University of Calgary at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy of confirmatory testing (seated saline infusion test and the ultra low-dose ACTH stimulation test) (time frame: The total study timeline will occur over 66 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04422756, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.