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

NCT ID: NCT03362047

Last Updated: 2025-03-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

7 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-01

Study Completion Date

2024-08-14

Brief Summary

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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.

Detailed Description

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In this multi-center, randomized, open pilot study the therapeutic effect of two prarallel groups treated with either Riciguat or Macitentan shall be determined by evaluating the change in systolic and diastolic RV function within 12 weeks after first drug intake in order to plan a larger Phase II study.The method used to determine the RV function will be the "Conductance Method".

Conditions

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Pulmonary Arterial Hypertension (PAH)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Multicentre, randomized, prospective, open pilot study
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Riciguat Group

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.

Group Type EXPERIMENTAL

Riciguat Group

Intervention Type DRUG

Patients will be administered 12 weeks Riciguat

Macitentan Group

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.

Group Type EXPERIMENTAL

Macitentan Group

Intervention Type DRUG

Patients will be administered 12 weeks Macitentan

Interventions

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Riciguat Group

Patients will be administered 12 weeks Riciguat

Intervention Type DRUG

Macitentan Group

Patients will be administered 12 weeks Macitentan

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

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
* History of bronchial artery embolization
* smoker
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Philipps University Marburg

OTHER

Sponsor Role collaborator

University of Giessen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Werner Seeger, Prof

Role: PRINCIPAL_INVESTIGATOR

University Gießen

Locations

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Klinik III für Innere Medizin Herzzentrum der Universität zu Köln

Cologne, , Germany

Site Status

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

Giessen, , Germany

Site Status

Krankenhaus Neuwittelsbach, Innere Medizin II

München, , Germany

Site Status

Countries

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Germany

References

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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.

Reference Type BACKGROUND
PMID: 24355642 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24173272 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22730335 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26318161 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23883378 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22854298 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22912874 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12531727 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23397593 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15750042 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23233754 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15287080 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17080491 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26308684 (View on PubMed)

Other Identifiers

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2015-002835-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

250774

Identifier Type: -

Identifier Source: org_study_id

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