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

Primary Aldosteronism Clinical Trial

— RETAME-PA  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06108427
• Other study ID #: RETAME-PA
• Status: Not yet recruiting
• Phase: N/A
• Start date: March 2024
• Est. completion date: December 2025

Study information

• Verified date: January 2024
• Source: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
• Contact: Remi Goupil, MD MSc
• Phone: 1(514)338-2883
• Email: remi.goupil[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 58
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hyperaldosteronism
• Primary Aldosteronism

Intervention

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

Locations

Country	Name	City	State
Canada	Hôpital du Sacré-Coeur de Montréal	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with unsuppressed renin	Proportion of participants with plasma renin concentration >15 mIU/L or >10 ng/L, or plasma renin activity >1 ng/mL/h	12 months
Secondary	Relative change in renin levels from baseline	Relative change in renin levels from baseline	12 months
Secondary	Office-based systolic and diastolic BP	Office-based systolic and diastolic BP	12 months
Secondary	Central systolic and diastolic BP	Central systolic and diastolic BP	12 months
Secondary	Absolute change in left ventricular mass index from baseline	Absolute change in left ventricular mass index from baseline	12 months
Secondary	Defined daily dose of mineralocorticoid receptor antagonists	Defined daily dose of mineralocorticoid receptor antagonists	12 months
Secondary	Defined daily dose of all antihypertensive medications (including mineralocorticoid receptor antagonists)	Defined daily dose of all antihypertensive medications (including mineralocorticoid receptor antagonists)	12 months
Secondary	Health-related quality of life (SF-36 questionnaire)	Health-related quality of life (SF-36 questionnaire): Score of 0 to 100 with highest better	12 months
Secondary	Health-related quality of life (primary aldosteronism-specific questionnaire)	Health-related quality of life (primary aldosteronism-specific questionnaire): Score of 0 to 112 with highest worse	12 months
Secondary	Albumin/creatinine ratio	Albumin/creatinine ratio	12 months
Secondary	Serum potassium levels	Serum potassium levels	12 months
Secondary	Change in eGFR	Change in eGFR	12 months
Secondary	Proportion of participants with MRA discontinuation, switch or dose-reduction due to side effects or hyperkalemia	Proportion of participants with MRA discontinuation, switch or dose-reduction due to side effects or hyperkalemia	12 months
Secondary	Acute kidney injury (>50% increase in serum creatinine)	>50% increase in serum creatinine	12 months
Secondary	Number of participants with progression towards kidney failure	Number of participants with sustained eGFR loss = 40%, kidney replacement therapy or death from renal failure	12 months
Secondary	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	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
Secondary	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)	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
Secondary	All-cause hospitalisation	All-cause hospitalisation	12 months
Secondary	All-cause mortality	All-cause mortality	12 months