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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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-scannin

Detailed Summary:
Sponsor: Radboud University

Current Primary Outcome: Daily Defined Doses of antihypertensive medication [ Time Frame: assessed after 1 year of follow-up ]

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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Total cost of diagnosis and management [ Time Frame: assessed after 1 year follow-up ]
    Costs of the diagnostic course and the first year of treatment after determination of subtype of PA will be calculated prospectively and bottom-up for each participant. This includes costs of CT, AVS (hardware, rent of facility, lab determinations, cost of personnel), operation, outpatient clinic visits, medication and lab controls for potassium and creatinine. Long term costs will be extrapolated from the first year's results for an average life expectancy and a predefined discounting rate.
  • Health Related Quality of Life [ Time Frame: assesed before treatment, at 6 months and at 12 months follow-up ]
    The quality of life in our patients may be influenced in different ways. AVS is more invasive and more burdensome to the patient than CT; the same holds for surgery as compared to medical treatment; on the other hand, more intense and prolonged (lifelong) antihypertensive drug treatment may be associated with more side effects. We suggested to explore these issues, using the . EQ-5D (European Quality of Life-5 Dimensions) and the SF-36 (Medical Outcomes Study 36-Item Short-Form Health Survey). This will allow for a detailed analysis of the impact of the two strategies on the quality of life of the patients.
  • Potassium level [ Time Frame: assesed before treatment and after 1 year follow-up ]
    Serum potassium levels will be determined before Adx or start of MRA and one year later. Potassium levels will be compared between the two arms of the study.
  • Result of a sodium loading test [ Time Frame: assessed after 1 year follow-up ]
    This test, which is the reference test for the existence of PA, will be performed only in patients that have undergone adrenalectomy because in these patients PA is expected to be cured after adrenalectomy with hence a normal result of this test. The test will be performed 1 year after operation after interruption of medication that interferes with the measurement of aldosterone levels. The proportion of patients who were cured (i.e. with normal saline loading test) will be compared between the CT- and the AVS-group.
  • Post-hoc analysis: medication dosage [ Time Frame: assessed after 1 year follow-up ]
    A post-hoc analysis on medication use will be performed using different outcome measures. Required antihypertensive medication one year after the (start of) treatment, expressed in multiples of the recommended starting dose and fraction of the recommended maximum dose, will be analysed.


Original Secondary Outcome:

  • Total cost of diagnosis and management [ Time Frame: assessed after 1 year follow-up ]
    Costs of the diagnostic course and the first year of treatment after determination of subtype of PA will be calculated prospectively and bottom-up for each participant. This includes costs of CT, AVS (hardware, rent of facility, lab determinations, cost of personnel), operation, outpatient clinic visits, medication and lab controls for potassium and creatinine. Long term costs will be extrapolated from the first year's results for an average life expectancy and a predefined discounting rate.
  • Health Related Quality of Life [ Time Frame: assesed before treatment, at 6 months and at 12 months follow-up ]
    The quality of life in our patients may be influenced in different ways. AVS is more invasive and more burdensome to the patient than CT; the same holds for surgery as compared to medical treatment; on the other hand, more intense and prolonged (lifelong) antihypertensive drug treatment may be associated with more side effects. We suggested to explore these issues, using the . EQ-5D and the SF-36. This will allow for a detailed analysis of the impact of the two strategies on the quality of life of the patients.
  • Potassium level [ Time Frame: assesed before treatment and after 1 year follow-up ]
    Serum potassium levels will be determined before Adx or start of MRA and one year later. Potassium levels will be compared between the two arms of the study.
  • Result of a sodium loading test [ Time Frame: assessed after 1 year follow-up ]
    This test, which is the reference test for the existence of PA, will be performed only in patients that have undergone adrenalectomy because in these patients PA is expected to be cured after adrenalectomy with hence a normal result of this test. The test will be performed 1 year after operation after interruption of medication that interferes with the measurement of aldosterone levels. The proportion of patients who were cured (i.e. with normal saline loading test) will be compared between the CT- and the AVS-group.


Information By: Radboud University

Dates:
Date Received: March 30, 2010
Date Started: July 2010
Date Completion:
Last Updated: July 15, 2015
Last Verified: July 2015