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

Study Overview
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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.

Official Title
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Untersuchung Des Einflusses PAH-spezifischer Medikation Auf Die rechtsventrikuläre Funktion Bei Patienten Mit Pulmonaler Arterieller Hypertonie (PAH) Unter Basalen Bedingungen

Conditions
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Pulmonary Arterial Hypertension (PAH)

Intervention / Treatment
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* Drug: Riciguat Group
* Drug: Macitentan Group


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicentre, randomized, prospective, open pilot study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Riciguat Group<br>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<br>* Patients will be administered 12 weeks Riciguat<br>|
| Experimental: Macitentan Group<br>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<br>* Patients will be administered 12 weeks Macitentan<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recruitability | The feasible to include 30 patients within 12 months will be assessed by descripitve statistic | 12 months | 
| feasibility to set up a larger phase II study | The feasibility to set up a larger phase II study with this study setting and design will be assessed by descripitve statistic | 24 months | 
| RV contractility | Percent change in RV contractility (= end-systolic elastance, EES), RV, Methods: RV Catheterisation and Conductance Catherterisation. | 12 weeks | 
| Collection of Adverse Events | number of participants with adverse events (all) assessed by CTCAE v4.0 | 12 weeks |