SPIRO-First: A Pragmatic Primary Care-Embedded Pilot Trial of Renin-Guided First-Line Antihypertensive Therapy

Phase 4Not Yet RecruitingNCT07687160

Ottawa Hospital Research Institute30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypertension

Interventions

Spironolactone (drug)DRUG

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.

Candesartan 8mgDRUG

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.

Hydrochlorothiazide (HCTZ) 25 milligrams.DRUG

Amlodipine (5mg)DRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 12 months following activation of all participating study sites

Secondary Outcomes

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.

Time frame: 12 months

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.

Time frame: 12 months

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.

Time frame: 12 months

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).

Time frame: 12 months

SECONDARY OUTCOME #5: Antihypertensive Washout Completion Rate

Proportion of participants for whom the protocol-specified antihypertensive washout procedures are successfully completed when applicable

Time frame: 12 months

SECONDARY OUTCOME #6: Ambulatory Blood Pressure Monitoring Completion Rate

Proportion of randomized participants who successfully complete ambulatory blood pressure monitoring (ABPM) according to the study protocol.

Time frame: 12 weeks

SECONDARY OUTCOME #7: Protocol Adherence Rate

Proportion of randomized participants completing assigned study treatment and the Week 12 outcome assessment procedures according to the study protocol.

Time frame: 12 weeks

SECONDARY OUTCOME #8: Study Completion Rate

Proportion of randomized participants completing the Week 12 end-of-study assessment.

Time frame: 12 weeks

SECONDARY OUTCOME #9: Reasons for Non-participation, Treatment Discontinuation, and Study Withdrawal

Frequency and categorized reasons for declining participation, treatment discontinuation, and withdrawal from the study.

Time frame: 12 months

SECONDARY OUTCOME #10: Data Completeness

Proportion of required study data fields completed without missing or invalid values.

Time frame: 12 weeks

SECONDARY OUTCOME #11: Primary Care Clinician Satisfaction With Patient Participation

Primary care clinician satisfaction with their patients' participation in the study, assessed using a post-study questionnaire.

Time frame: end of study (at 12 months)

SECONDARY OUTCOME #12: Primary Care Clinician Satisfaction With Study Communication

Primary care clinician satisfaction regarding communication on participant progress and handover of care following study completion, assessed using a post-study questionnaire.

Time frame: end of study (at 12 months)

SECONDARY OUTCOME #13: Primary Care Clinician Engagement

Proportion of participating primary care clinicians who continue referring potentially eligible participants throughout the study period.

Time frame: 12 months

SPIRO-First: A Pragmatic Primary Care-Embedded Pilot Trial of Renin-Guided First-Line Antihypertensive Therapy

Overview

Conditions

Interventions

Eligibility

Locations (4)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts