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

NCT01096654 | Completed Phase 3

• 1 other identifier: avs-ct1
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hyperaldosteronism

Keywords

endocrine hypertension; primary hyperaldosteronism; aldosterone; aldosterone-producing adenoma; bilateral adrenal hyperplasia; computed tomography; adrenal vein sampling

Outcome Measures

Primary Outcomes (1)

• Daily Defined Doses of antihypertensive medication

  The main study parameter is the quantity of antihypertensive drugs patients are using to obtain target blood pressure, expressed in Daily Defined Doses (DDD)16. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It provides a fixed unit of measurement independent of price and dosage form (e.g. tablet strength) enabling the researcher to assess trends in drug consumption and to perform comparisons between population groups.

  assessed after 1 year of follow-up

Secondary Outcomes (5)

• Total cost of diagnosis and management

  assessed after 1 year follow-up

• Health Related Quality of Life

  assesed before treatment, at 6 months and at 12 months follow-up

• Potassium level

  assesed before treatment and after 1 year follow-up

• Result of a sodium loading test

  assessed after 1 year follow-up

• Post-hoc analysis: medication dosage

  assessed after 1 year follow-up

Study Arms (2)

CT-scan

ACTIVE COMPARATOR

In this group treatment will be based on the outcome of the CT-scan only. Patients will be treated by adrenalectomy (Adx) if an unilateral lesion is visible on the CT-scan and the contralateral gland is normal. If bilateral lesions, bilateral enlargement or symmetric normal adrenal glands are present patients will be treated by the mineralocorticoid receptor antagonist (MRA)

Other: Ct-scan or adrenal vein sampling

Adrenal Vein Sampling

ACTIVE COMPARATOR

This group will be treated according to the results of the adrenal vein sampling only. Adrenal vein sampling will be performed under the continuous infusion of ACTH (adrenocorticotropic hormone). A cortisol ratio ≥ 3 between the adrenal vein and the inferior vena cava is set as the criterium for successful cannulation. The criterium for lateralization is a aldosterone/cortisol ratio ≥ 4 between the adrenal veins and a lower aldosterone/cortisol ratio in the contralateral adrenal vein than in the inferior vena cava. If AVS fails patients will be treated according to the CT-findings as described in the group with CT-scan only. Patients with a successful AVS will be treated by Adrenalectomy if unilateral production of aldosterone is shown. If no unilateral aldosterone production is present, i.e. the aldosterone/cortisol ratio is less than 4, patients will be treated by MRA.

Other: Ct-scan or adrenal vein sampling

Interventions

Ct-scan or adrenal vein sampling OTHER

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.

Adrenal Vein Sampling; CT-scan

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

UMC St. radboud

Nijmegen, Gelderland, 6525 GA, Netherlands

Location

Related Publications (6)

• Kempers MJ, Lenders JW, van Outheusden L, van der Wilt GJ, Schultze Kool LJ, Hermus AR, Deinum J. Systematic review: diagnostic procedures to differentiate unilateral from bilateral adrenal abnormality in primary aldosteronism. Ann Intern Med. 2009 Sep 1;151(5):329-37. doi: 10.7326/0003-4819-151-5-200909010-00007.

  PMID: 19721021 BACKGROUND

• Mulatero P, Bertello C, Sukor N, Gordon R, Rossato D, Daunt N, Leggett D, Mengozzi G, Veglio F, Stowasser M. Impact of different diagnostic criteria during adrenal vein sampling on reproducibility of subtype diagnosis in patients with primary aldosteronism. Hypertension. 2010 Mar;55(3):667-73. doi: 10.1161/HYPERTENSIONAHA.109.146613. Epub 2010 Feb 1.

  PMID: 20124107 BACKGROUND

• Kline GA, Harvey A, Jones C, Hill MH, So B, Scott-Douglas N, Pasieka JL. Adrenal vein sampling may not be a gold-standard diagnostic test in primary aldosteronism: final diagnosis depends upon which interpretation rule is used. Variable interpretation of adrenal vein sampling. Int Urol Nephrol. 2008;40(4):1035-43. doi: 10.1007/s11255-008-9441-9. Epub 2008 Aug 12.

  PMID: 18696249 BACKGROUND

• Stewart PM, Allolio B. Adrenal vein sampling for Primary Aldosteronism: time for a reality check. Clin Endocrinol (Oxf). 2010 Feb;72(2):146-8. doi: 10.1111/j.1365-2265.2009.03714.x. Epub 2009 Sep 21. No abstract available.

  PMID: 19769616 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 DERIVED

• Dekkers T, Prejbisz A, Kool LJS, Groenewoud HJMM, Velema M, Spiering W, Kolodziejczyk-Kruk S, Arntz M, Kadziela J, Langenhuijsen JF, Kerstens MN, van den Meiracker AH, van den Born BJ, Sweep FCGJ, Hermus ARMM, Januszewicz A, Ligthart-Naber AF, Makai P, van der Wilt GJ, Lenders JWM, Deinum J; SPARTACUS Investigators. Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial. Lancet Diabetes Endocrinol. 2016 Sep;4(9):739-746. doi: 10.1016/S2213-8587(16)30100-0. Epub 2016 Jun 17.

  PMID: 27325147 DERIVED

MeSH Terms

Conditions

Hyperaldosteronism; Adrenocortical Adenoma

Condition Hierarchy (Ancestors)

Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Adrenal Cortex Diseases

Study Officials

• Jacob Deinum, Dr.

  UCM St. Radboud

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2010
• First Posted: March 31, 2010
• Study Start: July 1, 2010
• Primary Completion: July 1, 2015
• Study Completion: July 1, 2015
• Last Updated: July 16, 2015

Record last verified: 2015-07

Locations

NL (1)