The goal of this clinical trial is to determine whether a renin-guided antihypertensive treatment strategy is feasible to implement in community primary care clinics and to explore whether spironolactone improves blood pressure control in adults with low-renin hypertension.
The main questions it aims to answer are:
Is it feasible to identify, recruit, randomize, and follow adults with low-renin hypertension in a pragmatic primary care-based clinical trial?
Does first-line treatment with spironolactone result in greater reductions in ambulatory blood pressure compared with standard first-line antihypertensive therapy among adults with low-renin hypertension?
Researchers will compare spironolactone 25 mg daily with standard first-line antihypertensive therapy (candesartan, hydrochlorothiazide, or amlodipine) to determine whether spironolactone provides better blood pressure control in adults with low-renin hypertension.
Participants will:
Undergo blood pressure assessments, blood tests, and ambulatory blood pressure monitoring (ABPM) to determine eligibility.
Be randomly assigned to receive either spironolactone or a standard first-line antihypertensive medication for 12 weeks.
Complete follow-up visits and laboratory testing to monitor blood pressure response, kidney function, electrolyte levels, medication adherence, and side effects.
Undergo repeat blood pressure measurements and ABPM at the end of the study.
Age ≥18 years.
Under the care of a primary care clinician in Ontario.
Standardized office systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg.
Mean daytime baseline ABPM systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg.
Standardized office systolic blood pressure >170 mmHg if untreated OR >150 mmHg if receiving one antihypertensive medication.
Known diagnosis of PA requiring specialist-directed management.
Known secondary hypertension requiring disease-specific therapy.
Current use of MR antagonists.
Parallel
Spironolactone (drug)
DrugSpironolactone 25 mg daily: Spironolactone is a widely available and inexpensive MR antagonist medication which blocks the action of aldosterone. Spironolactone is the most commonly recommended drug for the treatment of primary aldosteronism given its efficacy in improving blood pressure and reducing cardiovascular and kidney disease risk for this patient population, with 25 mg being the standard starting dose.
Candesartan 8mg
DrugComparator medications were selected because they represent common guideline-recommended first-line antihypertensive therapies from mechanistically distinct drug classes routinely used in contemporary primary care practice and hypertension guidelines. Doses were selected based on equivalent defined daily doses (DDD). The purpose of including multiple comparator therapies is to emulate real-world first-line prescribing practices in primary care rather than compare spironolactone against a single mechanistic alternative.
Hydrochlorothiazide (HCTZ) 25 milligrams.
DrugComparator medications were selected because they represent common guideline-recommended first-line antihypertensive therapies from mechanistically distinct drug classes routinely used in contemporary primary care practice and hypertension guidelines. Doses were selected based on equivalent defined daily doses (DDD). The purpose of including multiple comparator therapies is to emulate real-world first-line prescribing practices in primary care rather than compare spironolactone against a single mechanistic alternative.
Amlodipine (5mg)
DrugComparator medications were selected because they represent common guideline-recommended first-line antihypertensive therapies from mechanistically distinct drug classes routinely used in contemporary primary care practice and hypertension guidelines. Doses were selected based on equivalent defined daily doses (DDD). The purpose of including multiple comparator therapies is to emulate real-world first-line prescribing practices in primary care rather than compare spironolactone against a single mechanistic alternative.
PRIMARY OUTCOME: Recruitment Rate of Randomized Participants per Month
Recruitment rate, defined as the average number of participants randomized per month during the recruitment period following activation of all participating study sites. Recruitment feasibility will be assessed by calculating the number of participants randomized each month over the 12-month recruitment period.
SECONDARY OUTCOME #1: Number of Potentially Eligible Participants Identified
Number of potentially eligible participants identified by participating primary care clinicians and referred for study screening.
SECONDARY OUTCOME #2: Eligibility Rate
Eligibility rate, defined as the proportion of screened participants who meet all study eligibility criteria. Calculated as the number of eligible participants divided by the number of screened participants.
SECONDARY OUTCOME #3: Recruitment Acceptance Rate
Recruitment acceptance rate, defined as the proportion of eligible participants who provide informed consent and undergo randomization. Calculated as the number of randomized participants divided by the number of eligible participants.
SECONDARY OUTCOME #4: Prevalence of Suppressed Renin Physiology
Proportion of screened participants with suppressed renin physiology, defined as a direct renin concentration \<6 ng/L (\<10 mU/L).
Exploratory Outcome #1 (Blood pressure outcomes): Change in Mean Daytime Systolic Blood Pressure
Change in mean daytime systolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) from baseline to Week 12.
Exploratory Outcome #2 (Blood pressure outcomes): Change in Mean Daytime Diastolic Blood Pressure
Change in mean daytime diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) from baseline to Week 12.
Exploratory Outcome 3 (Blood pressure outcomes): Change in Mean 24-Hour Systolic Blood Pressure
Change in mean 24-hour systolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) from baseline to Week 12.
Exploratory Outcome 4 (Blood pressure outcomes): Change in Mean 24-Hour Diastolic Blood Pressure
Change in mean 24-hour diastolic blood pressure measured by ambulatory blood pressure monitoring (ABPM) from baseline to Week 12.
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Ottawa Hospital Research Institute
Lead sponsor
The Ottawa Hospital
Collaborator
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