Effects of Mineralocorticoid and AT-1 Receptor Antagonism on the Aldosterone-Renin Ratio (ARR) In Primary Aldosteronism Patients (EMIRA Study): Rationale and Design
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Aldosterone to renin ratio (ARR)
研究概览
简要总结
Current guidelines recommend withdrawal of treatments that affect the aldosterone/renin ratio (ARR) when screening for primary aldosteronism (PA). However, abandonment of mineralocorti-coid-receptor antagonist (MRA) and/or blockers of the renin-angiotensin system can deteriorate control of blood pressure (BP) and hypokalemia. Thus, in consecutive patients with an unambiguous diagnosis of PA in wash-out from confounding treatments and subtyped by AVS, the investigators have compared within-patient the plasma aldosterone and active renin concentration, and the ARR values, measured at baseline, and after a one-month treatment with MRA alone and combined with an AT-1 receptor blocker (ARB). Patients on a regular salt intake have been treated with canrenone (50-100 mg orally) for 1 month, after which olmesartan (10 or 20 mg orally) has been added for another month with up-titration of both treatments over the first 2 weeks to control BP and hypokalemia, however maintaining background therapy. The biochemical variables and the ARR have been assessed in an identical manner at baseline values and after each month of treatment. The investigators calculated that with a sample size of 40 patients the study will have a 95% power to show a clinically significant 20% change in the ARR at an 5% alfa-value using a two-sided paired t-test. Hence, this study will allow to determine if an MRA alone, or added to an ARB at doses that control BP and hypokalemia, affect or not the ARR, thus allow to establish if these agents can be administered or must be forbidden during the screening of PA.
详细描述
Primary aldosteronism (PA) is a common form of hypertension caused by aldosterone secretion inappropriate for blood pressure (BP) and volume status. It involves over 11% of the patients referred to specialized hypertension centres, about one fifth of those with drug-resistant hypertension and even a large proportion of the hypertensive patients seen in general practice. The only main subtype of PA that can be unambiguously diagnosed based on post-adrenalectomy using a "five corners" approach is aldosterone-producing adenoma (APA).
In patients undergoing screening for PA the current guidelines recommend pharmacological wash-out or, more correctly, switch to antihypertensive therapy not influencing the values of plasma aldosterone concentration (PAC) and direct renin concentration (DRC) and therefore of the aldosterone/renin ratio (ARR). This therapy generally entails a long-acting calcium channel blocker, alone or in combination with an alpha-blocker. However, a significant proportion of hypertensive patients, about one third, require more complex therapies to maintain acceptable BP levels. In addition, a proportion, estimated at around 10% of patients with PA, have hypertension resistant to common antihypertensives, as shown in the PATWAY-2 study. Noteworthy, these patients usually exibit a BP lowering response to mineralocorticoid-receptor antagonists (MRAs).
MRAs act as diuretics and therefore stimulate the renin-angiotensin-aldosterone system (RAAS), which might confound the results of the diagnostic tests, increasing renin and therefore reducing the ARR. This is considered to increase the rate of false negative tests. Moreover, some data suggest that MRA could inhibit the synthesis of aldosterone. However, this remains contentious as there are no prospective studies in this regard. Therefore, the use of MRAs, which can effectively control BP and hypokalemia during the PA screening is generally discouraged, despite the lack of solid prospective studies in this regard.
The stimulation of SRAA, if it actually occurs in a patient with PA, could be controlled, or prevented, by the use of an angiotensin AT-1 receptor blocker.
Therefore, the investigators set out a prospective observational study aimed at investigating, with a within-patient comparison, the values of PAC, DRC, ARR, serum potassium, in addition to blood pressure, in patients unambigously diagnosed with PA, who underwent screening and subtyping in washout from confounding treatments according to the current guidelines, with the values produced by treatment with MRA (canrenone) given alone or in combination with an angiotensin AT-1 receptor blocker (olmesartan).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Crossover
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age 18 - 75 years;
- •diagnosis of Aldosterone Producing Adenoma (APA);
- •written informed consent.
排除标准
- •refusal to participate to the study;
- •history of intolerance or allergy to canrenone or ARB.
研究组 & 干预措施
Patients with primary aldosteronism (PA)
After two biochemical and clinical evaluations under baseline conditions PA patients will be treated with canrenone 50-100 mg orally once a day.
After one month of such therapy they will undergo the a clinical and biochemical evaluation (FW1). After, they will continue with a combination therapy with canrenone, plus olmesartan starting with 10 mg a day for oral administration, a dose that can be doubled, if necessary, to achieve normotension.
At the end of the second month of the double therapy, patients will undergo a biochemical re-evaluation at the Center of Hypertension (FW2).
干预措施: canrenone 50-100 mg orally once a day (Drug)
Patients with primary aldosteronism (PA)
After two biochemical and clinical evaluations under baseline conditions PA patients will be treated with canrenone 50-100 mg orally once a day.
After one month of such therapy they will undergo the a clinical and biochemical evaluation (FW1). After, they will continue with a combination therapy with canrenone, plus olmesartan starting with 10 mg a day for oral administration, a dose that can be doubled, if necessary, to achieve normotension.
At the end of the second month of the double therapy, patients will undergo a biochemical re-evaluation at the Center of Hypertension (FW2).
干预措施: olmesartan 10-20 mg orally once a day (Drug)
结局指标
主要结局
Aldosterone to renin ratio (ARR)
时间窗: one month
ARR measured as ng/mIU after treatment with canrenone, or olmesartan on top of canrenone
次要结局
- Blood pressure(one month)
- Serum potassium levels(one month)
研究者
Gian Paolo Rossi, MD, FAHA, FACC
Professor
University Hospital Padova