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

NCT07687160 | Not Yet Recruiting Phase 4

• 1 other identifier: 7198
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

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.

Conditions

Hypertension

Keywords

hypertension; Renin-Guided Therapy; Antihypertensive treatment; Spironolactone; Precision Medicine; Primary aldosteronism

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months following activation of all participating study sites

Secondary Outcomes (13)

• SECONDARY OUTCOME #1: Number of Potentially Eligible Participants Identified

  12 months

• SECONDARY OUTCOME #2: Eligibility Rate

  12 months

• SECONDARY OUTCOME #3: Recruitment Acceptance Rate

  12 months

• SECONDARY OUTCOME #4: Prevalence of Suppressed Renin Physiology

  12 months

• SECONDARY OUTCOME #5: Antihypertensive Washout Completion Rate

  12 months

Other Outcomes (24)

• Exploratory Outcome #1 (Blood pressure outcomes): Change in Mean Daytime Systolic Blood Pressure

  Baseline to Week 12

• Exploratory Outcome #2 (Blood pressure outcomes): Change in Mean Daytime Diastolic Blood Pressure

  Baseline to Week 12

• Exploratory Outcome 3 (Blood pressure outcomes): Change in Mean 24-Hour Systolic Blood Pressure

  Baseline to Week 12

Study Arms (2)

Spironolactone

EXPERIMENTAL

Spironolactone 25 mg daily

Drug: Spironolactone (drug)

Standard first-line antihypertensive therapy

ACTIVE COMPARATOR

Participants randomized to standard therapy will undergo secondary randomization to candesartan (8 mg daily), hydrochlorothiazide (25 mg daily), or amlodipine (5 mg daily)

Drug: Candesartan 8mg; Drug: Hydrochlorothiazide (HCTZ) 25 milligrams.; Drug: Amlodipine (5mg)

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.

Spironolactone

Candesartan 8mg DRUG

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.

Standard first-line antihypertensive therapy

Hydrochlorothiazide (HCTZ) 25 milligrams. DRUG

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.

Standard first-line antihypertensive therapy

Amlodipine (5mg) DRUG

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.

Standard first-line antihypertensive therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• The Ottawa Hospital: collaborator

Study Sites (3)

The Ottawa Hospital

Ottawa, Ontario, K1H 7W9, Canada

Location

Ottawa Nurse Practitioner-Led Clinic

Ottawa, Ontario, K1L 8L8, Canada

Location

St-Isidore Médical

Saint Isidore, Ontario, K0C 2B0, Canada

Location

MeSH Terms

Conditions

Hypertension; Hyperaldosteronism

Interventions

Spironolactone; Pharmaceutical Preparations; candesartan; Hydrochlorothiazide; Amlodipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Sharon Johnston, MD

  Institut du Savoir Montfort

  PRINCIPAL INVESTIGATOR

• Gregory L Hundemer, MD

  The Ottawa Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gregory L Hundemer, MD

CONTACT

(613) 738-8400; ghundemer@toh.ca

Deena Fremont, MSc

CONTACT

dfremont@ohri.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinician Scientist

Model Details: Pragmatic open-label pilot trial conducted in community primary care clinics

Study Record Dates

• First Submitted: June 12, 2026
• First Posted: July 7, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: July 13, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)