SPARTACUS: Subtyping Primary Aldosteronism: a Randomized Trial Comparing Adrenal Vein Sampling and Computed Tomography Scan.

Towards Cost-effective Management of Patients With Hypertension Due to Primary Aldosteronism: Adrenal Vein Sampling or Ct-scan?

Rationale: Primary hyperaldosteronism (PA) is the most frequent form of secondary hypertension. In PA autonomous hypersecretion of aldosterone by one or both adrenal glands causes hypertension that is often refractory to treatment. PA is usually caused by either a unilateral aldosterone-producing (micro)adenoma (APA) or by bilateral adrenal hyperplasia (BAH). Distinction between APA and BAH is critical since the former is treated with the aim of cure by adrenalectomy, and the latter by mineralocorticoid receptor antagonists. This distinction can be made by adrenal vein sampling (AVS), as recommended by The Endocrine Society 2008 guideline or by CT-scanning, as is common practice in the Netherlands. AVS is invasive, demands great skill, and is expensive, while CT-scanning is non-invasive, easy and cheap, but might be less accurate. However, the advantage of AVS has never been demonstrated in prospective randomized studies. Here we propose to perform a prospective, randomized, multicenter study that compares effectiveness of AVS with effectiveness of CT-scanning for the diagnosis of PA subtype.

Objective: To assess the quantity of antihypertensive medication needed in order to normalize blood pressure in patients who have been managed for PA according to either AVS or CT-scan. Secondary objectives: to assess potassium, costs of management and quality of life.

Study design: Prospective, randomized trial in a multi-centre setting. Two hundred patients will be recruited within two years. Follow-up will be one year after (start of) treatment.

Study population: Adult patients with therapy-resistant hypertension, with or without hypokalemia, caused by PA.

Intervention: Patients will be randomized to undergo either adrenal CT-scanning or AVS (with pre-AVS adrenal CT-scanning for phlebography). The result of either of these tests will determine the course of action: adrenalectomy for adenoma or MRAs for bilateral hyperplasia.

Main study parameters/endpoints: The quantity of antihypertensive drugs patients are using to obtain target blood pressure, expressed in Daily Defined Dosages, is used as the main study parameter. There is no criterion standard for accuracy of the diagnosis of PA-subtype, but we assume that if treatment is based on a more accurate diagnosis, treatment is more effective. The most important secondary endpoints are the costs of the diagnostic course and long-term medical treatment and the quality of life as assessed by a validated questionnaire.

Inclusion Criteria:

• Legally capacitated;
• ≥ 18 years of age;
• Diagnosed with hypertension that is difficult to treat (blood pressure > 140/90 mmHg in spite of two antihypertensive drugs in adequate doses), or accompanied by hypokalemia, either spontaneous or induced by use of diuretics;
• patients must have a positive result on a sodium loading test (as recommended in the Endocrine Society Guideline), i.e. insufficient suppression of aldosterone.
• Cooperating patient who is willing to undergo adrenal surgery in case of an adenoma or lateralized aldosterone secretion, who is able to comply with the study protocol and who is willing to give written informed consent.

Exclusion Criteria:

• Unsuitability for or objection to undergo AVS, CT or adrenal surgery.(including pregnancy);
• Glucocorticoid remediable aldosteronism or adrenal carcinoma;
• Severe or terminal co-morbidity which seriously interferes with possible treatment or health related quality of life;
• Requirement of certain medication that interacts with the prescribed treatments in this protocol or that can cause hypertension as an important side-effect e.g. glucocorticoids. Patients will only be excluded as the medication cannot be stopped or altered.