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

NCT03362047 | Completed Phase 2

• 2 other identifiers: 2507742015-002835-17
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Pulmonary Arterial Hypertension (PAH)

Outcome Measures

Primary Outcomes (1)

• RV function

  Evaluation of the therapeutic effect of both treatment groups as measured by the change in systolic and diastolic RV function within 12 weeks after starting medication to plan a larger Phase II study. Methods: RV Catheterisation and Conductance Catherterisation.

  12 weeks

Secondary Outcomes (4)

• recruitability

  12 months

• feasibility to set up a larger phase II study

  24 months

• RV contractility

  12 weeks

• Collection of Adverse Events

  12 weeks

Study Arms (2)

Riciguat Group

EXPERIMENTAL

15 PAH patients will be administered Riciguat according to standard of care. RV function will be evaluated 90 mintutes after first medication intake and 12 weeks after first medication intake.

Drug: Riciguat Group

Macitentan Group

EXPERIMENTAL

15 PAH patients will be administered Macitentan according to standard of care. RV function will be evaluated 90 mintutes after first medication intake and 12 weeks after first medication intake.

Drug: Macitentan Group

Interventions

Riciguat Group DRUG

Patients will be administered 12 weeks Riciguat

Riciguat Group

Macitentan Group DRUG

Patients will be administered 12 weeks Macitentan

Macitentan Group

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female and male patients, 18 years ≤ age ≤ 85 years
• Diagnosis of Pulmonary Hypertension Group 1 according to Nizza Definition (PAH) confirmed by invasive methods, WHO functional class II and III
• Existing clinical need to repeat a right ventricular catheter examination (as recommended by the current "Kölner Konsensuskonferenz")
• Ability to understand study goals and agree to study participation
• Hemodynamic criteria of ventricular catheter examination:
• Pulmonary vascular resistance (PVR)\> 240 dyn x sec x cm-5
• Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mmHg
• Clinical need to receive treatment with a drug approved for the treatment of PAH for the first time
• Potentially fertile women must agree to use highly effective methods of contraception, either through abstinence or the use of at least two methods of contraception from the date of consent until one month after the end of the study. An effective pregnancy protection consists in the combination of a hormonal contraceptive (oral, injectable or implant) and a barrier method (condom or diaphragm with a vaginal spermicide)
• Written consent to the clinical trial

You may not qualify if:

• Existing therapy with positive inotropic drugs such as Catecholamines (including norepinephrine, dobutamine, suprarenin)
• Pregnancy or breastfeeding
• General contraindication for examinations to be performed during the study
• Hypersensitivity to the active substances or to a constituent of the study medication (in particular lactose and soya)
• Simultaneous participation in another medical therapy study
• Simultaneous participation in another non-drug study that would preclude participation in this study
• Participation within one month after completing another therapy study
• Heavy liver function disorders
• Existing increase in liver aminotransferases (aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT))\> 3 × ULN
• Systolic blood pressure \<95 mmHg
• Pulmonary hypertension associated with idiopathic interstitial pneumonia (PH-IIP)
• anemia (Hb \<10 g / dl)
• Concomitant medication with potential interaction to macitentan and/or riociguat according to the IB
• Severe kidney dysfunction
• Severe hemoptysis

Sponsors & Collaborators

• University of Giessen: lead
• Philipps University Marburg: collaborator

Study Sites (3)

Klinik III für Innere Medizin Herzzentrum der Universität zu Köln

Cologne, D-50973, Germany

Location

Abteilung Pneumologie und Intensivmedizin der Medizinischen Klinik II, Uniklinik Gießen und Marburg Standort Gießen

Giessen, 35392, Germany

Location

Krankenhaus Neuwittelsbach, Innere Medizin II

München, 80639, Germany

Location

Related Publications (14)

• 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.

  PMID: 24355642 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.

  PMID: 24173272 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.

  PMID: 22730335 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.

  PMID: 26318161 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.

  PMID: 23883378 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.

  PMID: 22854298 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.

  PMID: 22912874 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.

  PMID: 12531727 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.

  PMID: 23397593 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.

  PMID: 15750042 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.

  PMID: 23233754 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.

  PMID: 15287080 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.

  PMID: 17080491 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.

  PMID: 26308684 BACKGROUND

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Werner Seeger, Prof

  University Gießen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicentre, randomized, prospective, open pilot study

Study Record Dates

• First Submitted: November 22, 2017
• First Posted: December 5, 2017
• Study Start: March 1, 2018
• Primary Completion: July 3, 2024
• Study Completion: August 14, 2024
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be shared after end of study without limitation
• Access Criteria: e-mail to: Khodr.Tello@innere.med.uni-giessen.de

Locations

DE (3)