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

Overview

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.

Interventions

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

Primary outcome measures

• Proportion of participants with unsuppressed renin [Time frame: 12 months]

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Canada · 1 center

• Hôpital du Sacré-Coeur de Montréal — Montreal

Publications

• 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

Identifiers

NCT: NCT06108427 · RETAME-PA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗