(RIGHT HEART III Study - Right Ventricular Hemodynamic Evaluation and Response to Treatment)

Summary

Pilot study to determine the therapeutic effect of two prarallel groups treated with either Riciguat or Macitentan, evaluated by the change in systolic and diastolic RV function within 12 weeks after first drug intake in order to plan a larger Phase II study.

Timeline

Start

2018-03-01

Primary completion

2024-07-03

Completion

2024-08-14

Publications

• Background McGoon MD, Benza RL, Escribano-Subias P, Jiang X, Miller DP, Peacock AJ, Pepke-Zaba J, Pulido T, Rich S, Rosenkranz S, Suissa S, Humbert M. Pulmonary arterial hypertension: epidemiology and registries. J Am Coll Cardiol. 2013 Dec 24;62(25 Suppl):D51-9. doi: 10.1016/j.jacc.2013.10.023.
• Background Peacock AJ, Crawley S, McLure L, Blyth KG, Vizza CD, Poscia R, Francone M, Iacucci I, Olschewski H, Kovacs G, Vonk Noordegraaf A, Marcus JT, van de Veerdonk MC, Oosterveer FP. Changes in right ventricular function measured by cardiac magnetic resonance imaging in patients receiving pulmonary arterial hypertension-targeted therapy: the EURO-MR study. Circ Cardiovasc Imaging. 2014 Jan;7(1):107-14. doi: 10.1161/CIRCIMAGING.113.000629. Epub 2013 Oct 30.
• Background Borgdorff MA, Bartelds B, Dickinson MG, Boersma B, Weij M, Zandvoort A, Sillje HH, Steendijk P, de Vroomen M, Berger RM. Sildenafil enhances systolic adaptation, but does not prevent diastolic dysfunction, in the pressure-loaded right ventricle. Eur J Heart Fail. 2012 Sep;14(9):1067-74. doi: 10.1093/eurjhf/hfs094. Epub 2012 Jun 22.
• Background Galie N, Humbert M, Vachiery JL, Gibbs S, Lang I, Torbicki A, Simonneau G, Peacock A, Vonk Noordegraaf A, Beghetti M, Ghofrani A, Gomez Sanchez MA, Hansmann G, Klepetko W, Lancellotti P, Matucci M, McDonagh T, Pierard LA, Trindade PT, Zompatori M, Hoeper M. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J. 2015 Oct;46(4):903-75. doi: 10.1183/13993003.01032-2015. Epub 2015 Aug 29.
• Background Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ; PATENT-1 Study Group. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013 Jul 25;369(4):330-40. doi: 10.1056/NEJMoa1209655.
• Background Kojonazarov B, Sydykov A, Pullamsetti SS, Luitel H, Dahal BK, Kosanovic D, Tian X, Majewski M, Baumann C, Evans S, Phillips P, Fairman D, Davie N, Wayman C, Kilty I, Weissmann N, Grimminger F, Seeger W, Ghofrani HA, Schermuly RT. Effects of multikinase inhibitors on pressure overload-induced right ventricular remodeling. Int J Cardiol. 2013 Sep 10;167(6):2630-7. doi: 10.1016/j.ijcard.2012.06.129. Epub 2012 Jul 31.
• Background Lang M, Kojonazarov B, Tian X, Kalymbetov A, Weissmann N, Grimminger F, Kretschmer A, Stasch JP, Seeger W, Ghofrani HA, Schermuly RT. The soluble guanylate cyclase stimulator riociguat ameliorates pulmonary hypertension induced by hypoxia and SU5416 in rats. PLoS One. 2012;7(8):e43433. doi: 10.1371/journal.pone.0043433. Epub 2012 Aug 17.
• Background Brimioulle S, Wauthy P, Ewalenko P, Rondelet B, Vermeulen F, Kerbaul F, Naeije R. Single-beat estimation of right ventricular end-systolic pressure-volume relationship. Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1625-30. doi: 10.1152/ajpheart.01023.2002. Epub 2003 Jan 16.
• Background Herberg U, Gatzweiler E, Breuer T, Breuer J. Ventricular pressure-volume loops obtained by 3D real-time echocardiography and mini pressure wire-a feasibility study. Clin Res Cardiol. 2013 Jun;102(6):427-38. doi: 10.1007/s00392-013-0548-3. Epub 2013 Feb 9.
• Background Wilkins MR, Paul GA, Strange JW, Tunariu N, Gin-Sing W, Banya WA, Westwood MA, Stefanidis A, Ng LL, Pennell DJ, Mohiaddin RH, Nihoyannopoulos P, Gibbs JS. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med. 2005 Jun 1;171(11):1292-7. doi: 10.1164/rccm.200410-1411OC. Epub 2005 Mar 4.
• Background Nagendran J, Sutendra G, Paterson I, Champion HC, Webster L, Chiu B, Haromy A, Rebeyka IM, Ross DB, Michelakis ED. Endothelin axis is upregulated in human and rat right ventricular hypertrophy. Circ Res. 2013 Jan 18;112(2):347-54. doi: 10.1161/CIRCRESAHA.111.300448. Epub 2012 Dec 10.
• Background Muller HH, Schafer H. A general statistical principle for changing a design any time during the course of a trial. Stat Med. 2004 Aug 30;23(16):2497-508. doi: 10.1002/sim.1852.
• Background Timmesfeld N, Schafer H, Muller HH. Increasing the sample size during clinical trials with t-distributed test statistics without inflating the type I error rate. Stat Med. 2007 May 30;26(12):2449-64. doi: 10.1002/sim.2725.
• Background Galie N, Barbera JA, Frost AE, Ghofrani HA, Hoeper MM, McLaughlin VV, Peacock AJ, Simonneau G, Vachiery JL, Grunig E, Oudiz RJ, Vonk-Noordegraaf A, White RJ, Blair C, Gillies H, Miller KL, Harris JH, Langley J, Rubin LJ; AMBITION Investigators. Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension. N Engl J Med. 2015 Aug 27;373(9):834-44. doi: 10.1056/NEJMoa1413687.

Drugs

Indications