ARNI Versus plAcebo in Patients With Congenital sYStemic Right Ventricle Heart Failure

• Status: Not yet recruiting
• Trial end date: 2024-11-12
• Target enrollment: 0
• Participant gender: All

Summary

This study is a prospective monocentric, randomized, double-blind, placebo-controlled, crossover clinical trial to assess the efficacy of Sacubitril/Valsartan over placebo in improving exercise capacity and neurohormonal activation in adults with moderate to severe systemic RV dysfunction and NYHA class II or III symptoms.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Montreal Heart Institute
• Collaborator: Novartis Pharmaceuticals
• Treatments: Valsartan

Criteria

Inclusion Criteria:

• Age > or egal18 years with clinical follow-up at the Montreal Heart Institute Adult Congenital Heart Center

• Systemic right ventricle (transposition of great vessels and atrial switch or congenitally corrected transposition of great vessels)

• Moderate to severe systemic right ventricle dysfunction by transthoracic echocardiography (TTE) or right ventricle ejection fraction (RVEF) <40% by MRI

• NYHA Functional class II-III symptoms or peak exercise capacity <80% of predicted on a previous standard treadmill exercise stress test (usually done every two years in our congenital clinic).

• Ability to provide informed consent to the study

• Access or own a telephone and/or access to internet connection for teleconference call

• Own a mailing address to receive the medication by post (FedEx or Dicom)

• Able to perform self-measurement of the blood pressure using Upper Arm Digital Blood Pressure Monitor as recommended by Hypertension Canada.

Exclusion Criteria:

• Participation in a clinical trial of an investigational drug, concurrently, or within the last 30 days prior enrolment

• Planned cardiac surgery (e.g., severe tricuspid regurgitation with planned tricuspid valve replacement or repair)

• Previous cardiac transplantation, or on heart transplant wait list

• Myocardial infarction, stroke, or open-heart surgery in the previous 4 weeks

• NYHA Functional class I or IV symptoms

• Symptomatic hypotension (fainting, dizziness, lightheadedness, blurred vision, weakness, fatigue, nausea, palpitations, and headache) with a systolic blood pressure <100 mmHg at screening, or asymptomatic <90 mmHg at screening

• eGFR <30 mL/min/1.73 m2

• Reduction in eGFR >35% from screening to randomization

• Potassium >5.2 mmol/L at screening or >5.4 mmol/L at randomization

• Known history of angioedema related to previous ACEI or ARB therapy or patients with a history of hereditary or idiopathic angioedema.

• Patients who require concomitant treatment with an angiotensin converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) or a renin inhibitor for other indication than heart failure

• Evidence of hepatic disease as determined by any one of the following: serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) values exceeding 3x upper limit of normal, bilirubin >1.5 mg/dl at screening.

• Unacceptable side effects with ACE-inhibitors or ARBs

• Patient known with bilateral renal artery stenosis

• Cyanosis; substantial left-to-right shunting (Qp/Qs >1.5); severe mitral, aortic, or pulmonary regurgitation; systemic or pulmonary inflow obstruction with a peak velocity >1.5 m/s by transthoracic echocardiography; and severe outflow tract obstruction with a peak systolic gradient >80 mm Hg.

• Inability to provide informed consent

• Unable to exercice

• Pregnant or planned pregnancy during the study

• Breastfeeding

• Severe pulmonary hypertension defined as pulmonary pressure egal or superior to systemic pressure