REnin-guided TherApy With MinEralocorticoid Receptor Antagonists in Primary Aldosteronism - Feasibility Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Proportion of participants with unsuppressed renin
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Renin-guided arm
Renin levels will be measured prior to each follow-up appointment and MRA therapy will be titrated to achieve renin unsuppression and normokalemia. Once this is achieved, any other class of antihypertensive drugs mais be used to achieve normal BP levels.
干预措施: Renin measurements (Other)
Renin-blinded arm
No measurements of renin levels will be allowed during follow-up. MRA therapy will be titrated to achieve normokalemia. Once this is achieved, any other class of antihypertensive drugs mais be used to achieve normal BP levels.
结局指标
主要结局
Proportion of participants with unsuppressed renin
时间窗: 12 months
Proportion of participants with plasma renin concentration \>15 mIU/L or \>10 ng/L, or plasma renin activity \>1 ng/mL/h
次要结局
- Relative change in renin levels from baseline(12 months)
- Acute kidney injury (>50% increase in serum creatinine)(12 months)
- Central systolic and diastolic BP(12 months)
- Defined daily dose of all antihypertensive medications (including mineralocorticoid receptor antagonists)(12 months)
- Albumin/creatinine ratio(12 months)
- All-cause hospitalisation(12 months)
- Office-based systolic and diastolic BP(12 months)
- Absolute change in left ventricular mass index from baseline(12 months)
- Defined daily dose of mineralocorticoid receptor antagonists(12 months)
- Health-related quality of life (SF-36 questionnaire)(12 months)
- Health-related quality of life (primary aldosteronism-specific questionnaire)(12 months)
- Change in eGFR(12 months)
- Number of participants with symptomatic orthostatic hypotension, dizziness, light headedness, injurious falls, syncope or any unexpected event that the attending physician believes could be attributed to the intervention(12 months)
- All-cause mortality(12 months)
- Serum potassium levels(12 months)
- Number of participants with cardiovascular adverse events: cardiovascular mortality, myocardial infarction, stroke, heart failure requiring hospitalisation, peripheral artery disease requiring revascularisation (composite and individual categories)(12 months)
- Proportion of participants with MRA discontinuation, switch or dose-reduction due to side effects or hyperkalemia(12 months)
- Number of participants with progression towards kidney failure(12 months)
研究者
Remi Goupil, MD MSc
Associate Professor of Clinic
Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal