Prospective Evaluation of Confirmatory Testing For Primary Aldosteronism

Study Overview
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Brief Summary
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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
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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.

Official Title
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Prospective Evaluation of Confirmatory Testing For Primary Aldosteronism

Conditions
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Primary Aldosteronism

Intervention / Treatment
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* Diagnostic Test: Seated intravenous saline infusion test
* Diagnostic Test: Ultra low-dose ACTH stimulation test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Diagnostic Test: Seated intravenous saline infusion 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.|
|Diagnostic Test: Ultra low-dose ACTH stimulation 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 the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The optimal cutoff value for confirmatory testing using clinically-important thresholds | Plasma aldosterone | The total study timeline will occur over 66 months. | 
| The optimal cutoff value for confirmatory testing using clinically-important thresholds | Aldosterone-to-renin ratio | The total study timeline will occur over 66 months. |