~36 spots leftby Dec 2026

Renin-Guided MRA Therapy for Primary Aldosteronism

(RETAME-PA Trial)

Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Centre Integre Universitaire de Sante et Services Sociaux du Nord de l'ile de Montreal
Must be taking: Mineralocorticoid antagonists
Must not be taking: Potassium-sparing diuretics
Disqualifiers: Kidney problems, High potassium, others
No Placebo Group
Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

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.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but you cannot have used mineralocorticoid receptor antagonists or potassium-sparing diuretics in the past 3 months. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug for primary aldosteronism?

Research shows that mineralocorticoid receptor antagonists (MRAs), like those used in the treatment, can help lower blood pressure and reduce cardiovascular risks in patients with primary aldosteronism. Additionally, MRAs have been shown to improve vascular function, which is important for heart health.12345

Is Renin-Guided MRA Therapy for Primary Aldosteronism safe for humans?

Mineralocorticoid receptor antagonists (MRAs), like eplerenone and spironolactone, have been used safely in humans for conditions like heart failure and high blood pressure, though they can sometimes cause high potassium levels. Newer nonsteroidal MRAs, such as AZD9977 and finerenone, have shown to be generally well-tolerated with fewer risks of high potassium, making them potentially safer options.24567

How does the drug Aldactone differ from other treatments for primary aldosteronism?

Aldactone (spironolactone) is unique because it uses renin measurements to guide its dosage, aiming to optimize treatment by targeting unsuppressed renin levels, which can help reduce blood pressure and proteinuria in primary aldosteronism patients. This approach is different from standard treatments that do not typically use renin levels to adjust therapy.23489

Research Team

Eligibility Criteria

Adults diagnosed with Primary Aldosteronism who need long-term treatment with mineralocorticoid receptor antagonists (MRA) can join. They must have low renin levels and not be pregnant, breastfeeding, or have used MRA recently. People with severe kidney issues, high potassium levels, or those unable to consent are excluded.

Inclusion Criteria

I have been diagnosed with pulmonary arterial hypertension.
Your blood test shows low levels of a hormone called renin before starting the treatment.
I am over 18 years old.
See 1 more

Exclusion Criteria

Your blood potassium level has been higher than 4.8 mmol/L in the past 3 months.
I have not used potassium-sparing diuretics or mineralocorticoid receptor antagonists in the last 3 months.
Stopping my current medications for a new treatment is considered unsafe for me.
See 5 more

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MRA therapy, with adjustments based on renin levels for the renin-guided group, and without renin level checks for the renin-blinded group

12 months
Regular follow-up visits for monitoring and dose adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of renin levels, blood pressure, and side effects

4 weeks

Treatment Details

Interventions

  • Renin measurements (Other)
Trial OverviewThe trial is testing if adjusting the dose of MRA based on renin hormone levels is more effective than standard care in controlling aldosterone action. Participants will be randomly assigned to either a 'renin-guided' group or a 'standard care' group for comparison over 12 months.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: Renin-guided armExperimental Treatment1 Intervention
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.
Group II: Renin-blinded armActive Control1 Intervention
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.

Find a Clinic Near You

Research Locations NearbySelect from list below to view details:
Hôpital du Sacré-Coeur de MontréalMontréal, Canada
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Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials
17
Patients Recruited
4,600+

Findings from Research

Primary aldosteronism (PA) is a significant cause of hypertension, affecting 5-10% of patients, and is associated with a cardiovascular risk profile that is double that of essential hypertension, highlighting the importance of screening for PA in all hypertensive patients.
Treatment options for PA include laparoscopic adrenalectomy for unilateral cases and low-dose mineralocorticoid receptor antagonists (MRAs) for bilateral cases, with new MRAs in development to improve efficacy and reduce side effects.
Primary Aldosteronism: Present and Future.Funder, JW.[2019]
Eplerenone Improves Vascular Endothelial Function in Patients with Primary Aldosteronism: A Pilot Study.Kurozumi, A., Okada, Y., Tanaka, Y.[2021]
Using Renin Activity to Guide Mineralocorticoid Receptor Antagonist Therapy in Patients with Low Renin and Hypertension.Mansur, A., Vaidya, A., Turchin, A.[2023]
This study will evaluate the effects of mineralocorticoid-receptor antagonists (MRA) and angiotensin receptor blockers (ARB) on the aldosterone/renin ratio (ARR) in 40 patients diagnosed with primary aldosteronism (PA), aiming to determine if these treatments can be safely continued during screening without compromising blood pressure control or causing hypokalemia.
By comparing plasma aldosterone and active renin concentrations before and after one month of treatment with MRA alone and then with the addition of ARB, the study seeks to clarify whether these medications can be used during ARR testing, potentially improving patient management in PA.
Effects of mineralocorticoid and AT-1 receptor antagonism on the aldosterone-renin ratio (ARR) in primary aldosteronism patients (EMIRA Study): rationale and design.Rossitto, G., Cesari, M., Ceolotto, G., et al.[2020]
Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data.Pilz, S., Trummer, C., Verheyen, N., et al.[2018]
Effectiveness of nonsteroidal mineralocorticoid receptor antagonists in patients with diabetic kidney disease.Lerma, E., White, WB., Bakris, G.[2023]
Safety, Tolerability, and Pharmacokinetics of the Mineralocorticoid Receptor Modulator AZD9977 in Healthy Men: A Phase I Multiple Ascending Dose Study.Whittaker, A., Kragh, ÅM., Hartleib-Geschwindner, J., et al.[2021]
The ratios of aldosterone / plasma renin activity (ARR) versus aldosterone / direct renin concentration (ADRR).Glinicki, P., Jeske, W., Bednarek-Papierska, L., et al.[2022]
Feasibility of Screening Primary Aldosteronism by Aldosterone-to-Direct Renin Concentration Ratio Derived from Chemiluminescent Immunoassay Measurement: Diagnostic Accuracy and Cutoff Value.Li, T., Ma, Y., Zhang, Y., et al.[2022]

References

Primary Aldosteronism: Present and Future. [2019]
Eplerenone Improves Vascular Endothelial Function in Patients with Primary Aldosteronism: A Pilot Study. [2021]
Using Renin Activity to Guide Mineralocorticoid Receptor Antagonist Therapy in Patients with Low Renin and Hypertension. [2023]
Effects of mineralocorticoid and AT-1 receptor antagonism on the aldosterone-renin ratio (ARR) in primary aldosteronism patients (EMIRA Study): rationale and design. [2020]
Mineralocorticoid Receptor Blockers and Aldosterone to Renin Ratio: A Randomized Controlled Trial and Observational Data. [2018]
Effectiveness of nonsteroidal mineralocorticoid receptor antagonists in patients with diabetic kidney disease. [2023]
Safety, Tolerability, and Pharmacokinetics of the Mineralocorticoid Receptor Modulator AZD9977 in Healthy Men: A Phase I Multiple Ascending Dose Study. [2021]
The ratios of aldosterone / plasma renin activity (ARR) versus aldosterone / direct renin concentration (ADRR). [2022]
Feasibility of Screening Primary Aldosteronism by Aldosterone-to-Direct Renin Concentration Ratio Derived from Chemiluminescent Immunoassay Measurement: Diagnostic Accuracy and Cutoff Value. [2022]