HypertensionPhase 4SPIRO-FirstNCT07687160
SPIRO-First: A Pragmatic Primary Care-Embedded Pilot Trial of Renin-Guided First-Line Antihypertensive Therapy
A Phase 4 study testing Spironolactone (drug), Candesartan 8mg and Hydrochlorothiazide (HCTZ) 25 milligrams. in people with Hypertension, run by Ottawa Hospital Research Institute at 4 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- Spironolactone (drug), Candesartan 8mg and Hydrochlorothiazide (HCTZ) 25 milligrams.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 4 sitesCanada
- Study dates
- 1 Jan 2027to Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
4 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Deena Fremont, MSc contact
Canada4 sites
GMF Universitaire Laval
Laval, Quebec, H7M 3L9
Rémi Goupil, MD, 514 338 2883, remi.goupil@umontreal.ca
The Ottawa Hospital
Ottawa, Ontario, K1H 7W9
Gregory L Hundemer, MD, (613) 738-8400 ext. 81885, ghundemer@toh.ca
Ottawa Nurse Practitioner-Led Clinic
Ottawa, Ontario, K1L 8L8
Hoda Mankal, NP, (613) 366-4742, hmankal@ottawanplc.org
St-Isidore Médical
Saint Isidore, Ontario, K0C 2B0
Manon Denis-LeBlanc, MD, (613) 524-3225, manondenisleblanc@montfort.on.ca
About this study
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:
Read more
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
- Being tested
- Spironolactone (drug), Candesartan 8mg, Hydrochlorothiazide (HCTZ) 25 milligrams., Amlodipine (5mg)
- Keywords
- hypertension, Renin-Guided Therapy, Antihypertensive treatment, Spironolactone, Precision Medicine, Primary aldosteronism
- Medical subject headings
- Hypertension, Hyperaldosteronism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Experimental | Spironolactone 25 mg daily Receives: 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) Receives: Drug: Candesartan 8mg; Drug: Hydrochlorothiazide (HCTZ) 25 milligrams.; Drug: Amlodipine (5mg) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months following activation of all participating study sites
Secondary outcomes (13)
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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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
Measured: 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.
Measured: 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.
Measured: 12 weeks
SECONDARY OUTCOME #8: Study Completion Rate
Proportion of randomized participants completing the Week 12 end-of-study assessment.
Measured: 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.
Measured: 12 months
SECONDARY OUTCOME #10: Data Completeness
Proportion of required study data fields completed without missing or invalid values.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jul 2026
- Study start1 Jan 2027 (estimated)
- Primary completionAug 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pragmatic open-label pilot trial conducted in community primary care clinics
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- The Ottawa Hospital
- Responsible party
- Principal investigator, Greg Hundemer, Ottawa Hospital Research Institute
- Investigators
- Sharon Johnston, MD, Principal investigator, Institut du Savoir MontfortGregory L Hundemer, MD, Principal investigator, The Ottawa HospitalRémi Goupil, MD, Principal investigator, Université de Montréal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07687160
- Sponsor's protocol ID
- 7198
- Acronym
- SPIRO-First
- Status last verified
- Oct 2026
- First submitted
- 12 Jun 2026
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SPIRO-First: A Pragmatic Primary Care-Embedded Pilot Trial of Renin-Guided First-Line Antihypertensive Therapy
- ClinicalTrials.gov ID
- NCT07687160
- Acronym / sponsor ID
- SPIRO-First / 7198
- Conditions
- Hypertension
- Keywords
- hypertension, Renin-Guided Therapy, Antihypertensive treatment, Spironolactone, Precision Medicine, Primary aldosteronism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- The Ottawa Hospital
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- Aug 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 7 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Pragmatic open-label pilot trial conducted in community primary care clinics
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Experimental | Drug: Spironolactone (drug)Spironolactone 25 mg daily |
| Standard first-line antihypertensive therapy | Active comparator | Drug: Candesartan 8mg, Drug: Hydrochlorothiazide (HCTZ) 25 milligrams., Drug: Amlodipine (5mg)Participants randomized to standard therapy will undergo secondary randomization to candesartan (8 mg daily), hydrochlorothiazide (25 mg daily), or amlodipine (5 mg daily) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Spironolactone |
| Candesartan 8mgComparator 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. | Drug | Standard first-line antihypertensive therapy |
| 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 mechanistic alternative. | Drug | Standard first-line antihypertensive therapy |
| 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 mechanistic alternative. | Drug | Standard first-line antihypertensive therapy |
Primary outcome
PRIMARY OUTCOME: Recruitment Rate of Randomized Participants per Month
Time frame: 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.
13 secondary outcomes
SECONDARY OUTCOME #1: Number of Potentially Eligible Participants Identified
Time frame: 12 months
SECONDARY OUTCOME #2: Eligibility Rate
Time frame: 12 months
SECONDARY OUTCOME #3: Recruitment Acceptance Rate
Time frame: 12 months
SECONDARY OUTCOME #4: Prevalence of Suppressed Renin Physiology
Time frame: 12 months
SECONDARY OUTCOME #5: Antihypertensive Washout Completion Rate
Time frame: 12 months
SECONDARY OUTCOME #6: Ambulatory Blood Pressure Monitoring Completion Rate
Time frame: 12 weeks
SECONDARY OUTCOME #7: Protocol Adherence Rate
Time frame: 12 weeks
SECONDARY OUTCOME #8: Study Completion Rate
Time frame: 12 weeks
SECONDARY OUTCOME #9: Reasons for Non-participation, Treatment Discontinuation, and Study Withdrawal
Time frame: 12 months
SECONDARY OUTCOME #10: Data Completeness
Time frame: 12 weeks
SECONDARY OUTCOME #11: Primary Care Clinician Satisfaction With Patient Participation
Time frame: end of study (at 12 months)
SECONDARY OUTCOME #12: Primary Care Clinician Satisfaction With Study Communication
Time frame: end of study (at 12 months)
SECONDARY OUTCOME #13: Primary Care Clinician Engagement
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Deena Fremont, MSc contact
Sharon Johnston, MD principal investigator
Institut du Savoir Montfort
Gregory L Hundemer, MD principal investigator
The Ottawa Hospital
Rémi Goupil, MD principal investigator
Université de Montréal
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Spironolactone (drug), Candesartan 8mg and Hydrochlorothiazide (HCTZ) 25 milligrams. in people with Hypertension, run by Ottawa Hospital Research Institute at 4 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Gregory L Hundemer, MD ((613) 738-8400 ext. 81885, ghundemer@toh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
PRIMARY OUTCOME: Recruitment Rate of Randomized Participants per Month (time frame: 12 months following activation of all participating study sites). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.