Spironolactone Therapy in Chronic Stable Right HF Trial (STAR-HF)

University of Ottawa Heart Institute

Status and phase: Completed; Phase 4

Conditions: Pulmonary Hypertension, Primary, 2; Pulmonary Hypertension, Primary, 3; Pulmonary Hypertension, Primary, 4; Cardiomyopathy Right Ventricular; Chronic Right-Sided Heart Failure; Pulmonary Arterial Hypertension

Treatments: Radiation: PET/CT Scan: Two PET scans using 1. C-11 HED and 2. N-13 Ammonia or rubidium-82; Drug: Placebo; Drug: Spironolactone; Diagnostic Test: Cardiac MRI (Gadolinium enhanced)

Study type: Interventional

Funder types: Other

Identifiers

NCT03344159

20170694

Details and patient eligibility

About

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.

Full 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.

Enrollment: 15 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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15 participants in 2 patient groups, including a placebo group

Spironolactone

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Cardiac MRI (Gadolinium enhanced)

Drug: Spironolactone

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

Placebo

Placebo Comparator group

Description:

Participants with chronic right-sided heart failure will receive placebo daily for a total duration of 12 weeks.

Treatment:

Diagnostic Test: Cardiac MRI (Gadolinium enhanced)

Drug: Placebo

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