REnin-guided TherApy With MinEralocorticoid Receptor Antagonists in Primary Aldosteronism - Feasibility Study

Обзор

High blood pressure, or hypertension, can be caused by a condition called Primary Aldosteronism (PA), where the body produces too much of a hormone called aldosterone. People with PA have a higher risk of heart problems compared to those with regular high blood pressure. To treat PA, some patients need to take medicine called mineralocorticoid receptor antagonists (MRA) for the rest of their lives. While treatment with MRA is effective, it can have side effects like high levels of potassium in the blood, breast enlargement in men, menstrual problems in women, and reduced sex drive. Finding the right dose of MRA for each patient can be tricky. Recent observations suggest that when a hormone called renin goes up during MRA treatment, it might be a good sign. This is because renin is higher when the action of aldosterone is well blocked. But it's not certain if this happens because of the patient's unique characteristics or if it can truly be a way to know if the treatment is working. This study aims to find out if guiding MRA treatment with renin levels leads to more patients having unsuppressed renin levels compared to the standard of care. This is a multicentric pragmatic clinical trial. Patients with a new diagnosis of PA and low renin levels will be asked if there are willing to participate. Those with recent use of MRA, known MRA intolerance, severe kidney problems, or have high potassium levels will not be able to participate. Participants will be randomized into two groups: one group will have their MRA treatment adjusted based on renin levels (the "renin-guided" group), and the other group won't have renin levels checked during treatment (the "renin-blinded" group). Both groups will aim to have their blood pressure under control and potassium levels in the normal range. The main outcome is the proportion in each group with unsuppressed renin levels after 12 months. Other outcomes will be tested, such as changes in renin levels, how well the treatment works, and any safety concerns (like potassium levels, kidney function, side effects, and blood pressure changes). Different groups of patients will also be looked at separately, like men and women, different ages, races, and initial renin levels, to see if the approach works better for some people. This study will help find a safe and effective way to treat PA with MRA. Choosing the right dose of MRA is important to adequately block aldosterone but also to avoid side effects.

Вмешательства

• Другое Renin measurements
  Use of plasma renin measurements to guide MRA dosing, aiming for plasma renin unsuppression

Первичные конечные точки

• Proportion of participants with unsuppressed renin [Срок оценки: 12 months]

Вторичные конечные точки (12)

• Relative change in renin levels from baseline [Срок оценки: 12 months]
• Office-based systolic and diastolic BP [Срок оценки: 12 months]
• Central systolic and diastolic BP [Срок оценки: 12 months]
• Absolute change in left ventricular mass index from baseline [Срок оценки: 12 months]
• Defined daily dose of mineralocorticoid receptor antagonists [Срок оценки: 12 months]
• Defined daily dose of all antihypertensive medications (including mineralocorticoid receptor antagonists) [Срок оценки: 12 months]
• Health-related quality of life (SF-36 questionnaire) [Срок оценки: 12 months]
• Health-related quality of life (primary aldosteronism-specific questionnaire) [Срок оценки: 12 months]
• Albumin/creatinine ratio [Срок оценки: 12 months]
• Serum potassium levels [Срок оценки: 12 months]
• Change in eGFR [Срок оценки: 12 months]
• Proportion of participants with MRA discontinuation, switch or dose-reduction due to side effects or hyperkalemia [Срок оценки: 12 months]

Критерии участия

Критерии включения

• Over 18 years of age
• Diagnosis of PA, in accordance with clinical guidelines and local practice
• Suppressed plasma renin prior to treatment initiation (plasma renin concentration >15 mIU/L or >10 ng/L, or plasma renin activity >1 ng/mL/h)
• Planned long-term treatment with mineralocorticoid receptor antagonist

Критерии исключения

• Prior use of mineralocorticoid receptor antagonist or any potassium-sparing diuretics in the past 3 months
• Known intolerance or contraindication to mineralocorticoid receptor antagonist treatment
• eGFR < 30 ml/min/1.73m2 (past 3 months)
• Baseline serum potassium above > 4.8 mmol/L (past 3 months)
• Deemed medically unsafe to stop medications for the initiation of MRA as monotherapy
• Pregnancy or breastfeeding
• Participation in another study that is likely to affect renin or BP levels
• Inability to provide consent due to cognitive impairment and/or language barrier.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

Канада · 1 центр

• Hôpital du Sacré-Coeur de Montréal — Montreal

Публикации

• Merabtine A, Leung AA, Kline GA, Dubrofsky L, Hundemer GL, Goupil R. Renin-guided therapy with mineralocorticoid receptor antagonists in primary aldosteronism: feasibility study (RETAME-PA) - a clinical research protocol for a randomised controlled trial. BMJ Open. 2025 Dec 19;15(12):e111167. doi: 10.1136/bmjopen-2025-111167. PMID 41419284

Идентификаторы

NCT: NCT06108427 · RETAME-PA

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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