Spironolactone Therapy in Chronic Stable Right HF Trial

NCT03344159 | Completed Phase 4

• 1 other identifier: 20170694
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 12 weeks

Secondary Outcomes (8)

• Change in Cardiac Sympathetic Nervous System Activity

  Baseline to 12 weeks

• Change in Cardiac Autonomic Nervous System Function

  Baseline to 12 weeks

• Change in Systemic Sympathetic Activation

  Baseline to 12 weeks

• Change in Right Ventricle Structure

  Baseline to 12 weeks

• Change in Right Ventricle Function

  Baseline to 12 weeks

Other Outcomes (5)

• Change in Serum Aldosterone

  Baseline to 12 weeks

• Change in Six Minute walk test

  Baseline, 6 weeks, 12 weeks

• Change in NYHA function class

  baseline to 12 weeks

Study Arms (2)

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.

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.

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)

Interventions

Spironolactone DRUG

Spironolactone 12.5mg daily up to a maximum dose of 50 mg daily if tolerated for a total duration of 12 weeks.

Spironolactone

Placebo DRUG

Placebo daily for a total of duration of 12 weeks

Placebo

PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82 RADIATION

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.

Placebo; Spironolactone

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.

Placebo; Spironolactone

Eligibility Criteria

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

You may qualify if:

• 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:
• i) 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead

Study Sites (1)

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y4W7, Canada

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Lipodystrophy, Congenital Generalized, Type 3

Interventions

Spironolactone; Rubidium-82

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Patients will be blinded to study treatment for the duration of the study. Clinicians will also be blinded to study drug assignment. Evaluation of all study results will be done blinded to treatment randomization. Because of the double-blind design, safety laboratory tests, and monitoring of potential side effects will be performed for each participant for the duration of the trial, regardless of the treatment arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 28, 2017
• First Posted: November 17, 2017
• Study Start: April 1, 2018
• Primary Completion: August 30, 2022
• Study Completion: May 1, 2024
• Last Updated: May 6, 2026

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)