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

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.

Timeline

Start

2022-03-15

Primary completion

2023-03-01

Completion

2023-03-12

Outcome

Outcome not reported

Stopped: “The trial was prematurely terminated due to safety concerns.”

Publications

• Background Brida M, Diller GP, Gatzoulis MA. Systemic Right Ventricle in Adults With Congenital Heart Disease: Anatomic and Phenotypic Spectrum and Current Approach to Management. Circulation. 2018 Jan 30;137(5):508-518. doi: 10.1161/CIRCULATIONAHA.117.031544.
• Background Dore A, Houde C, Chan KL, Ducharme A, Khairy P, Juneau M, Marcotte F, Mercier LA. Angiotensin receptor blockade and exercise capacity in adults with systemic right ventricles: a multicenter, randomized, placebo-controlled clinical trial. Circulation. 2005 Oct 18;112(16):2411-6. doi: 10.1161/CIRCULATIONAHA.105.543470. Epub 2005 Oct 10.
• Background van der Bom T, Winter MM, Bouma BJ, Groenink M, Vliegen HW, Pieper PG, van Dijk AP, Sieswerda GT, Roos-Hesselink JW, Zwinderman AH, Mulder BJ. Effect of valsartan on systemic right ventricular function: a double-blind, randomized, placebo-controlled pilot trial. Circulation. 2013 Jan 22;127(3):322-30. doi: 10.1161/CIRCULATIONAHA.112.135392. Epub 2012 Dec 17.
• Background Zaragoza-Macias E, Zaidi AN, Dendukuri N, Marelli A. Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Apr 2;139(14):e801-e813. doi: 10.1161/CIR.0000000000000604.
• Background Reddy S, Bernstein D. Molecular Mechanisms of Right Ventricular Failure. Circulation. 2015 Nov 3;132(18):1734-42. doi: 10.1161/CIRCULATIONAHA.114.012975.
• Background Lluri G, Lin J, Reardon L, Miner P, Whalen K, Aboulhosn J. Early Experience With Sacubitril/Valsartan in Adult Patients With Congenital Heart Disease. World J Pediatr Congenit Heart Surg. 2019 May;10(3):292-295. doi: 10.1177/2150135119825599.
• Background Appadurai V, Thoreau J, Malpas T, Nicolae M. Sacubitril/Valsartan in Adult Congenital Heart Disease Patients With Chronic Heart Failure - A Single Centre Case Series and Call for an International Registry. Heart Lung Circ. 2020 Jan;29(1):137-141. doi: 10.1016/j.hlc.2018.12.003. Epub 2018 Dec 17.
• Background Maurer SJ, Pujol Salvador C, Schiele S, Hager A, Ewert P, Tutarel O. Sacubitril/valsartan for heart failure in adults with complex congenital heart disease. Int J Cardiol. 2020 Feb 1;300:137-140. doi: 10.1016/j.ijcard.2019.06.031. Epub 2019 Jun 13.
• Background Zandstra TE, Nederend M, Jongbloed MRM, Kies P, Vliegen HW, Bouma BJ, Tops LF, Schalij MJ, Egorova AD. Sacubitril/valsartan in the treatment of systemic right ventricular failure. Heart. 2021 Nov;107(21):1725-1730. doi: 10.1136/heartjnl-2020-318074. Epub 2021 Jan 15.
• Background Therrien J, Provost Y, Harrison J, Connelly M, Kaemmerer H, Webb GD. Effect of angiotensin receptor blockade on systemic right ventricular function and size: a small, randomized, placebo-controlled study. Int J Cardiol. 2008 Sep 26;129(2):187-92. doi: 10.1016/j.ijcard.2008.04.056. Epub 2008 Jul 30.
• Background Ezekowitz JA, O'Meara E, McDonald MA, Abrams H, Chan M, Ducharme A, Giannetti N, Grzeslo A, Hamilton PG, Heckman GA, Howlett JG, Koshman SL, Lepage S, McKelvie RS, Moe GW, Rajda M, Swiggum E, Virani SA, Zieroth S, Al-Hesayen A, Cohen-Solal A, D'Astous M, De S, Estrella-Holder E, Fremes S, Green L, Haddad H, Harkness K, Hernandez AF, Kouz S, LeBlanc MH, Masoudi FA, Ross HJ, Roussin A, Sussex B. 2017 Comprehensive Update of the Canadian Cardiovascular Society Guidelines for the Management of Heart Failure. Can J Cardiol. 2017 Nov;33(11):1342-1433. doi: 10.1016/j.cjca.2017.08.022. Epub 2017 Sep 6.

Drugs

Indications