Hypertension
Conditions
Keywords
hypertension, Renin-Guided Therapy, Antihypertensive treatment, Spironolactone, Precision Medicine, Primary aldosteronism
Brief summary
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.
Interventions
Spironolactone 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.
DRUGCandesartan 8mg
Comparator 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.
Comparator 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.
DRUGAmlodipine (5mg)
Comparator 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.
Sponsors
Ottawa Hospital Research Institute
The Ottawa Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pragmatic open-label pilot trial conducted in community primary care clinics
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years. 2. Under the care of a primary care clinician in Ontario. 3. Standardized office systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. 4. Mean daytime baseline ABPM systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg. 5. Treating primary care clinician has independently determined that initiation of antihypertensive pharmacotherapy is clinically indicated. 6. Either: * Not currently receiving antihypertensive therapy, OR * Receiving a single antihypertensive medication (ACE inhibitor, ARB, thiazide/thiazide-like diuretic, or calcium channel blocker) which the treating primary care clinician considers safe to discontinue for a 2-week washout period. 7. Suppressed renin defined as direct renin concentration \<6 ng/L (\<10 mU/L) measured under routine outpatient conditions. Suppressed renin was selected as the primary biologic enrichment criterion because it is the physiologic hallmark of sodium-retaining, aldosterone-mediated hypertension and is more pragmatically scalable in primary care than complex biochemical primary aldosteronism (PA) definitions. 8. In the opinion of the treating primary care clinician, outpatient participation in the study is appropriate.
Exclusion criteria
1. Standardized office systolic blood pressure \>170 mmHg if untreated OR \>150 mmHg if receiving one antihypertensive medication. 2. Known diagnosis of PA requiring specialist-directed management. 3. Known secondary hypertension requiring disease-specific therapy. 4. Current use of MR antagonists. 5. Known intolerance or contraindication to spironolactone, candesartan, hydrochlorothiazide, or amlodipine. 6. eGFR \<30 mL/min/1.73 m2. 7. Serum potassium ≥5.0 mmol/L. 8. Serum sodium \<135 mmol/L. 9. Pregnancy, breastfeeding, or intention to become pregnant during the study period. Women of childbearing potential must have a negative pregnancy test prior to randomization. 10. Participation in another interventional study likely to affect blood pressure. 11. Inability to provide consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PRIMARY OUTCOME: Recruitment Rate of Randomized Participants per Month | 12 months following activation of all participating study sites | 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
| Measure | Time frame | Description |
|---|---|---|
| SECONDARY OUTCOME #1: Number of Potentially Eligible Participants Identified | 12 months | Number of potentially eligible participants identified by participating primary care clinicians and referred for study screening. |
| SECONDARY OUTCOME #2: Eligibility Rate | 12 months | 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 | 12 months | 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 | 12 months | Proportion of screened participants with suppressed renin physiology, defined as a direct renin concentration \<6 ng/L (\<10 mU/L). |
| SECONDARY OUTCOME #5: Antihypertensive Washout Completion Rate | 12 months | Proportion of participants for whom the protocol-specified antihypertensive washout procedures are successfully completed when applicable |
| SECONDARY OUTCOME #6: Ambulatory Blood Pressure Monitoring Completion Rate | 12 weeks | Proportion of randomized participants who successfully complete ambulatory blood pressure monitoring (ABPM) according to the study protocol. |
| SECONDARY OUTCOME #7: Protocol Adherence Rate | 12 weeks | Proportion of randomized participants completing assigned study treatment and the Week 12 outcome assessment procedures according to the study protocol. |
| SECONDARY OUTCOME #8: Study Completion Rate | 12 weeks | Proportion of randomized participants completing the Week 12 end-of-study assessment. |
| SECONDARY OUTCOME #9: Reasons for Non-participation, Treatment Discontinuation, and Study Withdrawal | 12 months | Frequency and categorized reasons for declining participation, treatment discontinuation, and withdrawal from the study. |
| SECONDARY OUTCOME #10: Data Completeness | 12 weeks | Proportion of required study data fields completed without missing or invalid values. |
| SECONDARY OUTCOME #11: Primary Care Clinician Satisfaction With Patient Participation | end of study (at 12 months) | Primary care clinician satisfaction with their patients' participation in the study, assessed using a post-study questionnaire. |
| SECONDARY OUTCOME #12: Primary Care Clinician Satisfaction With Study Communication | end of study (at 12 months) | Primary care clinician satisfaction regarding communication on participant progress and handover of care following study completion, assessed using a post-study questionnaire. |
| SECONDARY OUTCOME #13: Primary Care Clinician Engagement | 12 months | Proportion of participating primary care clinicians who continue referring potentially eligible participants throughout the study period. |
Countries
Canada
Contacts
CONTACTGregory L Hundemer, MD
CONTACTDeena Fremont, MSc
PRINCIPAL_INVESTIGATORSharon Johnston, MD
Institut du Savoir Montfort
PRINCIPAL_INVESTIGATORGregory L Hundemer, MD
The Ottawa Hospital
Outcome results
None listed