Clinical trial NCT06108427: REnin-guided TherApy With MinEralocorticoid Receptor Antagonists in Primary Aldosteronism - Feasibility Study
Official title: REnin-guided TherApy With MinEralocorticoid Receptor Antagonists in Primary Aldosteronism - Feasibility Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Primary Aldosteronism
Lead sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
Sponsor class: OTHER
First posted: 2023-10-31
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Proportion of participants with unsuppressed renin
timeFrame: 12 months
Secondary outcomes:
measure: Relative change in renin levels from baseline
timeFrame: 12 months
measure: Office-based systolic and diastolic BP
timeFrame: 12 months
measure: Central systolic and diastolic BP
timeFrame: 12 months
measure: Absolute change in left ventricular mass index from baseline
timeFrame: 12 months
measure: Defined daily dose of mineralocorticoid receptor antagonists
timeFrame: 12 months
measure: Defined daily dose of all antihypertensive medications (including mineralocorticoid receptor antagonists)
timeFrame: 12 months
measure: Health-related quality of life (SF-36 questionnaire)
timeFrame: 12 months
measure: Health-related quality of life (primary aldosteronism-specific questionnaire)
timeFrame: 12 months
measure: Albumin/creatinine ratio
timeFrame: 12 months
measure: Serum potassium levels
timeFrame: 12 months
measure: Change in eGFR
timeFrame: 12 months
measure: Proportion of participants with MRA discontinuation, switch or dose-reduction due to side effects or hyperkalemia
timeFrame: 12 months
measure: Acute kidney injury (>50% increase in serum creatinine)
timeFrame: 12 months
measure: Number of participants with progression towards kidney failure
timeFrame: 12 months
measure: 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
timeFrame: 12 months
measure: 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)
timeFrame: 12 months
measure: All-cause hospitalisation
timeFrame: 12 months
measure: All-cause mortality
timeFrame: 12 months
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Hôpital du Sacré-Coeur de Montréal
state: Quebec
Study officials:
References: