Chronic Right-Sided Heart FailurePhase 4STAR-HFNCT03344159
Spironolactone Therapy in Chronic Stable Right HF Trial
A Phase 4 study testing Spironolactone, PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82 and Cardiac MRI (Gadolinium enhanced) in people with Chronic Right-Sided Heart Failure and Pulmonary Arterial Hypertension, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
Trial summary
The purpose of this study is to evaluate the safety, tolerability and mechanistic effects of spironolactone, an aldosterone receptor antagonist, on sympathetic nervous system activity and right heart function and remodeling in patients with chronic right heart failure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Right-Sided Heart Failure, Pulmonary Arterial Hypertension, Pulmonary Hypertension, Primary, 2
- What is being tested?
- Spironolactone, PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82 and Cardiac MRI (Gadolinium enhanced)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteCanada
- Study dates
- 1 Apr 2018to 1 May 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Provide a personally signed and dated inform consent form.
- Male or female ≥ 18 years.
- Able to comply with all study procedures.
- History of right heart failure (RHF) secondary to either:
- WHO, group 1 pulmonary arterial hypertension PAH OR ii) WHO group II PH with normal LV systolic function OR iii) WHO group III or IV PH OR iv) primary RV cardiomyopathy.
- Current NYHA II-IV
Show all 11Show fewer
- RV dysfunction as measured by 2D echocardiogram:
- i)defined as a tricuspid annular plane systolic excursion (TAPSE) <16 mm ii) and /or a two dimensional fractional area change <35% on screening echo plus
- NT-proBNP>400 pg/ml
- Chronic use of diuretics
- Clinical stability: defined as no need for increased diuretics, hospitalization or emergency room visit 3 months prior to enrollment
Who cannot join
- Patients on chronic MRA therapy or other potassium sparing diuretics.
- Baseline serum potassium>5 ummol/l.
- Estimated glomerular filtration rate <30 ml/min.
- LV ejection fraction <45%,
- Moderate or severe LV diastolic function,
- Moderate or severe aortic or valvular disease.
Show all 12Show fewer
- Patients requiring augmentation of diuretics or otherwise not meeting definition for clinical stability.
- Severe Liver Failure (Child-Pugh Class C)
- Claustrophobia or inability lie still in a supine position
- Patients with contraindications to either PET or CMR imaging
- Pregnancy or lactation.
- Unable to provide consent and comply with follow up visits.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to evaluate the safety, tolerability and mechanistic effects of spironolactone, an aldosterone receptor antagonist, on sympathetic nervous system activity and right heart function and remodeling in patients with chronic right heart failure.
Read the detailed description
This study is a phase 4, single center, randomized, double blind, placebo-controlled trial evaluating the safety, tolerability and mechanistic effects of spironolactone, an aldosterone antagonist, on neurohormonal activity and remodeling in patients with chronic right heart failure (RHF).
RHF is one of the most important predictors of prognosis in many cardiac disease states including pulmonary hypertension (PH), and left heart failure. Sympathetic nervous system activation plays an important role in the development and progression of heart failure. It remains to be determined whether there is a role for neurohormonal therapy in chronic right HF, but evidence points to the role of sympathetic nervous system stimulation and activation of the renin-angiotensin and aldosterone system as a contributor to progressive right heart failure.
The study will determine if treatment with spironolactone is associated with reduction in right ventricular wall stress. In addition, the study aims to evaluate the effects of spironolactone on cardiac sympathetic activity assessed by HED(11 C-hydroxy-ephedrine) retention on PET(positron emission tomography) imaging, and global autonomic function assessed by heart rate variability.
Approximately 30 patients with RHF will be randomized to receive either spironolactone daily or placebo.
- Conditions
- Chronic Right-Sided Heart Failure, Pulmonary Arterial Hypertension, Pulmonary Hypertension, Primary, 2, Pulmonary Hypertension, Primary, 3, Pulmonary Hypertension, Primary, 4, Cardiomyopathy Right Ventricular
- Being tested
- Spironolactone, Placebo, PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82, Cardiac MRI (Gadolinium enhanced)
- Keywords
- Mineralocorticoid receptor antagonist, Brain natriuretic peptide (BNP), Sympathetic Nervous System, Positron Emissions Tomography
- Medical subject headings
- Pulmonary Arterial Hypertension, Hypertension, Pulmonary, Lipodystrophy, Congenital Generalized, Type 3
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
Spironolactone 12.5mg daily up to a maximum dose of 50 mg daily if tolerated for a total duration of 12 weeks.
PlaceboDrug
Placebo daily for a total of duration of 12 weeks
PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82Radiation
At baseline and 12 weeks, all participants will undergo rest perfusion PET imaging according to standard protocols with either 82-Rb or N-13 NH3, followed by C-11 HED PET.
Cardiac MRI (Gadolinium enhanced)Diagnostic test
At baseline and 12 weeks all participants will undergo cMR to assess RV function and structure. We will acquire precontrast T2 and native T1 maps, and post gadolinium T1 maps.
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Experimental | Participants with chronic right-sided heart failure will receive spironolactone 12.5mg daily up to a maximum dose of 50 mg daily for a total duration of 12 weeks. Receives: Drug: Spironolactone; Radiation: PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82; Diagnostic Test: Cardiac MRI (Gadolinium enhanced) |
| Placebo | Placebo comparator | Participants with chronic right-sided heart failure will receive placebo daily for a total duration of 12 weeks. Receives: Drug: Placebo; Radiation: PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82; Diagnostic Test: Cardiac MRI (Gadolinium enhanced) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Ventricular Wall Stress
To determine if treatment with spironolactone is associated with a significant reduction in RV ventricular wall stress, as reflected by a reduction in serum NT-proBNP, in patients with chronic stable right HF when compared to placebo.
Measured: Baseline and 12 weeks
Secondary outcomes (8)
Change in Cardiac Sympathetic Nervous System Activity
Changes in cardiac sympathetic activity, as assessed by an increase in 11[C]-hydroxy-ephedrine (HED) retention by cardiac PET imaging.
Measured: Baseline to 12 weeks
Change in Cardiac Autonomic Nervous System Function
Heart rate variability
Measured: Baseline to 12 weeks
Change in Systemic Sympathetic Activation
Changes in plasma levels of epinephrine and norepinephrine
Measured: Baseline to 12 weeks
Change in Right Ventricle Structure
Changes in RV end-diastolic and end-systolic size.
Measured: Baseline to 12 weeks
Change in Right Ventricle Function
Changes in RV ejection fraction
Measured: Baseline to 12 weeks
Change in Right Ventricle areas of fibrosis
Changes in RV areas of fibrosis assessed with T1 weighted MR imaging.
Measured: Baseline to 12 weeks
Number of participants with treatment-related adverse events.
- incidence of worsening renal function (defined as a change in estimated glomerular filtration rate>30%). 2. Incidence of hyperkalemia (>4.5, 5 or 5.5 mmol/L)
Measured: number of adverse events from baseline to 12 weeks.
Change in Biomarkers of Fibrosis
Changes in biomarkers of fibrosis (ST2, PIINP, CITB, TIMP1, MMP-9)
Measured: Baseline to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2017
- Study start1 Apr 2018
- Primary completion30 Aug 2022
- Study completion1 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Right-Sided Heart FailureStudies of the same condition, open and under way.
- 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
- STAR-HF is a phase 4 single center, randomized, placebo controlled trial comparing spironolactone 12.5mg daily up to a maximum dose of 50 mg daily if tolerated to matching placebo.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03344159
- Sponsor's protocol ID
- 20170694
- Acronym
- STAR-HF
- Status last verified
- Jun 2024
- First submitted
- 28 Sep 2017
- Last updated
- 6 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: There is no plan to share individual participant data with researchers outside of Dr. Mielniczuk's research team.
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Spironolactone Therapy in Chronic Stable Right HF Trial
- ClinicalTrials.gov ID
- NCT03344159
- Acronym / sponsor ID
- STAR-HF / 20170694
- Conditions
- Chronic Right-Sided Heart Failure, Pulmonary Arterial Hypertension, Pulmonary Hypertension, Primary, 2, Pulmonary Hypertension, Primary, 3, Pulmonary Hypertension, Primary, 4, Cardiomyopathy Right Ventricular
- Keywords
- Mineralocorticoid receptor antagonist, Brain natriuretic peptide (BNP), Sympathetic Nervous System, Positron Emissions Tomography
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Study start
- 1 Apr 2018 (actual)
- Primary completion
- 30 Aug 2022 (actual)
- Study completion
- 1 May 2024 (actual)
- First posted
- 17 Nov 2017 (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 purpose of this study is to evaluate the safety, tolerability and mechanistic effects of spironolactone, an aldosterone receptor antagonist, on sympathetic nervous system activity and right heart function and remodeling in patients with chronic right heart failure.
Detailed description
This study is a phase 4, single center, randomized, double blind, placebo-controlled trial evaluating the safety, tolerability and mechanistic effects of spironolactone, an aldosterone antagonist, on neurohormonal activity and remodeling in patients with chronic right heart failure (RHF).
RHF is one of the most important predictors of prognosis in many cardiac disease states including pulmonary hypertension (PH), and left heart failure. Sympathetic nervous system activation plays an important role in the development and progression of heart failure. It remains to be determined whether there is a role for neurohormonal therapy in chronic right HF, but evidence points to the role of sympathetic nervous system stimulation and activation of the renin-angiotensin and aldosterone system as a contributor to progressive right heart failure.
The study will determine if treatment with spironolactone is associated with reduction in right ventricular wall stress. In addition, the study aims to evaluate the effects of spironolactone on cardiac sympathetic activity assessed by HED(11 C-hydroxy-ephedrine) retention on PET(positron emission tomography) imaging, and global autonomic function assessed by heart rate variability.
Approximately 30 patients with RHF will be randomized to receive either spironolactone daily or placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- STAR-HF is a phase 4 single center, randomized, placebo controlled trial comparing spironolactone 12.5mg daily up to a maximum dose of 50 mg daily if tolerated to matching placebo.
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Experimental | Drug: Spironolactone, Radiation: PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82, Diagnostic Test: Cardiac MRI (Gadolinium enhanced)Participants with chronic right-sided heart failure will receive spironolactone 12.5mg daily up to a maximum dose of 50 mg daily for a total duration of 12 weeks. |
| Placebo | Placebo comparator | Drug: Placebo, Radiation: PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82, Diagnostic Test: Cardiac MRI (Gadolinium enhanced)Participants with chronic right-sided heart failure will receive placebo daily for a total duration of 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Provide a personally signed and dated inform consent form.
- Male or female ≥ 18 years.
- Able to comply with all study procedures.
- History of right heart failure (RHF) secondary to either:
- Current NYHA II-IV
Key exclusion criteria (12 listed)
- Patients on chronic MRA therapy or other potassium sparing diuretics.
- Baseline serum potassium>5 ummol/l.
- Estimated glomerular filtration rate <30 ml/min.
- LV ejection fraction <45%,
- Moderate or severe LV diastolic function,
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 |
|---|---|---|
| SpironolactoneSpironolactone 12.5mg daily up to a maximum dose of 50 mg daily if tolerated for a total duration of 12 weeks. | Drug | Spironolactone |
| PlaceboPlacebo daily for a total of duration of 12 weeks | Drug | Placebo |
| PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82At baseline and 12 weeks, all participants will undergo rest perfusion PET imaging according to standard protocols with either 82-Rb or N-13 NH3, followed by C-11 HED PET. | Radiation | Placebo, Spironolactone |
| Cardiac MRI (Gadolinium enhanced)At baseline and 12 weeks all participants will undergo cMR to assess RV function and structure. We will acquire precontrast T2 and native T1 maps, and post gadolinium T1 maps. | Diagnostic test | Placebo, Spironolactone |
Primary outcome
Change in Ventricular Wall Stress
Time frame: Baseline and 12 weeks
To determine if treatment with spironolactone is associated with a significant reduction in RV ventricular wall stress, as reflected by a reduction in serum NT-proBNP, in patients with chronic stable right HF when compared to placebo.
8 secondary outcomes
Change in Cardiac Sympathetic Nervous System Activity
Time frame: Baseline to 12 weeks
Change in Cardiac Autonomic Nervous System Function
Time frame: Baseline to 12 weeks
Change in Systemic Sympathetic Activation
Time frame: Baseline to 12 weeks
Change in Right Ventricle Structure
Time frame: Baseline to 12 weeks
Change in Right Ventricle Function
Time frame: Baseline to 12 weeks
Change in Right Ventricle areas of fibrosis
Time frame: Baseline to 12 weeks
Number of participants with treatment-related adverse events.
Time frame: number of adverse events from baseline to 12 weeks.
Change in Biomarkers of Fibrosis
Time frame: Baseline to 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2026.
- Individual participant dataSharing planned: No. There is no plan to share individual participant data with researchers outside of Dr. Mielniczuk's research team.
Related trials for Chronic Right-Sided Heart Failure
Recruiting
Feasibility of the SCD in Cardiorenal Syndrome Patients Awaiting LVAD
Acute on Chronic Systolic Congestive Heart Failure, Cardiorenal Syndrome
RecruitingObservational study
The Prognostic Role and Diagnostic Efficacy of Exercise Right Heart Catheterization With a Simultaneous Echocardiography in Patients With Dyspnea on Exertion
Heart Failure With Preserved Ejection Fraction, Chronic Pulmonary Thromboembolism (Disorder)
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site 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, PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82 and Cardiac MRI (Gadolinium enhanced) in people with Chronic Right-Sided Heart Failure and Pulmonary Arterial Hypertension, run by Ottawa Heart Institute Research Corporation at 1 site 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 11 inclusion and 12 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: finished, as of the sponsor's last update on 6 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Ventricular Wall Stress (time frame: Baseline and 12 weeks). 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 6 May 2026.