Spironolactone Therapy in Chronic Stable Right HF Trial

NCT ID: NCT03344159

Last Updated: 2024-07-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-01
• Study Completion Date: 2024-05-01

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Spironolactone

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.

Group Type: EXPERIMENTAL

Spironolactone

Intervention Type: DRUG

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

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

Intervention Type: 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.

Cardiac MRI (Gadolinium enhanced)

Intervention Type: 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

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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-82

Intervention Type: 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.

Cardiac MRI (Gadolinium enhanced)

Intervention Type: 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.

Interventions

Spironolactone

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

Intervention Type: DRUG

Placebo

Placebo daily for a total of duration of 12 weeks

Intervention Type: DRUG

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

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.

Intervention Type: RADIATION

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.

Intervention Type: DIAGNOSTIC_TEST

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lisa Mielniczuk, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Locations

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

Countries

Canada

Other Identifiers

20170694

Identifier Type: -

Identifier Source: org_study_id