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

Обзор

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.

Вмешательства

• Препарат Spironolactone (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.
• Препарат Candesartan 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
• Препарат Hydrochlorothiazide (HCTZ) 25 milligrams.
  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
• Препарат Amlodipine (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

Первичные конечные точки

• PRIMARY OUTCOME: Recruitment Rate of Randomized Participants per Month [Срок оценки: 12 months following activation of all participating study sites]

Вторичные конечные точки (12)

• SECONDARY OUTCOME #1: Number of Potentially Eligible Participants Identified [Срок оценки: 12 months]
• SECONDARY OUTCOME #2: Eligibility Rate [Срок оценки: 12 months]
• SECONDARY OUTCOME #3: Recruitment Acceptance Rate [Срок оценки: 12 months]
• SECONDARY OUTCOME #4: Prevalence of Suppressed Renin Physiology [Срок оценки: 12 months]
• SECONDARY OUTCOME #5: Antihypertensive Washout Completion Rate [Срок оценки: 12 months]
• SECONDARY OUTCOME #6: Ambulatory Blood Pressure Monitoring Completion Rate [Срок оценки: 12 weeks]
• SECONDARY OUTCOME #7: Protocol Adherence Rate [Срок оценки: 12 weeks]
• SECONDARY OUTCOME #8: Study Completion Rate [Срок оценки: 12 weeks]
• SECONDARY OUTCOME #9: Reasons for Non-participation, Treatment Discontinuation, and Study Withdrawal [Срок оценки: 12 months]
• SECONDARY OUTCOME #10: Data Completeness [Срок оценки: 12 weeks]
• SECONDARY OUTCOME #11: Primary Care Clinician Satisfaction With Patient Participation [Срок оценки: end of study (at 12 months)]
• SECONDARY OUTCOME #12: Primary Care Clinician Satisfaction With Study Communication [Срок оценки: end of study (at 12 months)]

Критерии участия

Критерии включения

• 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.
• Treating primary care clinician has independently determined that initiation of antihypertensive pharmacotherapy is clinically indicated.
• 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.
• 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.
• In the opinion of the treating primary care clinician, outpatient participation in the study is appropriate.

Критерии исключения

• 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.
• Known intolerance or contraindication to spironolactone, candesartan, hydrochlorothiazide, or amlodipine.
• eGFR <30 mL/min/1.73 m2.
• Serum potassium ≥5.0 mmol/L.
• Serum sodium <135 mmol/L.
• Pregnancy, breastfeeding, or intention to become pregnant during the study period. Women of childbearing potential must have a negative pregnancy test prior to randomization.
• Participation in another interventional study likely to affect blood pressure.
• Inability to provide consent

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Канада · 3 центра

• The Ottawa Hospital — Ottawa
• Ottawa Nurse Practitioner-Led Clinic — Ottawa
• St-Isidore Médical — Saint Isidore

Идентификаторы

NCT: NCT07687160 · 7198

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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