Clinical trial NCT03344159: Spironolactone Therapy in Chronic Stable Right HF Trial
Official title: Spironolactone Therapy in Chronic Stable Right HF Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
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
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2017-11-17
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Change in Ventricular Wall Stress
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Change in Cardiac Sympathetic Nervous System Activity
timeFrame: Baseline to 12 weeks
measure: Change in Cardiac Autonomic Nervous System Function
timeFrame: Baseline to 12 weeks
measure: Change in Systemic Sympathetic Activation
timeFrame: Baseline to 12 weeks
measure: Change in Right Ventricle Structure
timeFrame: Baseline to 12 weeks
measure: Change in Right Ventricle Function
timeFrame: Baseline to 12 weeks
measure: Change in Right Ventricle areas of fibrosis
timeFrame: Baseline to 12 weeks
measure: Number of participants with treatment-related adverse events.
timeFrame: number of adverse events from baseline to 12 weeks.
measure: Change in Biomarkers of Fibrosis
timeFrame: Baseline to 12 weeks
Other outcomes:
measure: Change in Serum Aldosterone
timeFrame: Baseline to 12 weeks
measure: Change in Six Minute walk test
timeFrame: Baseline, 6 weeks, 12 weeks
measure: Change in NYHA function class
timeFrame: baseline to 12 weeks
measure: Change in Right heart failure Severity
timeFrame: Baseline to 12 weeks
measure: Clinical Outcomes
timeFrame: 12 weeks
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Lisa Mielniczuk, MD
role: PRINCIPAL_INVESTIGATOR
References: