Chronic Thromboembolic Pulmonary Hypertension, Primary Pulmonary Arterial Hypertension
Conditions
Keywords
pulmonary arterial hypertension, Chronic Thromboembolic Pulmonary Hypertension, riociguat, right heart function
Brief summary
This is an open-label, single-armed, prospective single-centre clinical study to evaluate the effect of riociguat on right heart size and function in patients with manifest PAH and CTEPH.
Detailed description
Right heart size and function are of utmost prognostic importance in PAH/CTEPH. RV performance measured by echocardiography and enlarged RA area have been shown to be independent prognostic factors in PAH. Recently, a retrospective single centre study has shown that riociguat treatment was associated with a significant reduction of RV and RA area after 3, 6 and 12 months compared to baseline. RA area significantly decreased after 12 months and RV systolic function assessed with tricuspid annular plane systolic excursion (TAPSE) improved after 6 and 12 months of riociguat therapy. The results were confirmed by a recent retrospective multicentre study. It is therefore reasonable to assume a beneficial effect of riociguat on right heart size and function. The primary efficacy endpoint in this study is the change in RV and RA area from baseline to 24 weeks. Treatment will be initiated and individually adjusted according to systolic blood pressure and tolerability. Patients who discontinue medication prematurely will be asked to continue with study assessments and perform study visits as outlined in the protocol. Medical examinations comprise medical history, physical examination, electrocardiogram (ECG), blood gas analyses, lung function tests, laboratory testing (including NT-proBNP), echocardiography at rest, and right heart catheterization (RHC) according to clinical practice of the PH centre. The prospective period of data collection comprises a 24-week study period a follow-up phase of about 30±7 days. Outcome (survival and transplant-free survival) of all patients will be assessed when the last patient has terminated his/her 24-week observation period.
Interventions
DRUGRiociguat
Treatment will be initiated and individually adjusted according to systolic blood pressure and tolerability. During the titration phase, each patient will be asked to measure their peripheral systolic blood pressure and the heart rate at home three times per day and document the values in the patient diary. The results will be examined by the investigator during each visit/phone call-visit. Provided that the systolic blood pressure is ≥ 95 mmHg measured at trough before intake of each dose and the patient has no signs or symptoms of hypotension, the dose of study medication will be titrated by +0.5 mg tid every 2 weeks until maximal tolerated dosage (maximal permitted dose: of 2.5 mg tid). After the titration period, blood pressure should be measured upon signs or symptoms of hypotension. Maintenance dose: The established individual dose should be maintained unless signs and symptoms of hypotension occur.
Sponsors
Heidelberg University
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. ≥18 years of age at time of inclusion. 2. Male and female patients with symptomatic PAH with a mean pulmonary artery pressure (mPAP) \>20 mmHg and pulmonary vascular resistance (PVR) ≥2 Wood Units (WU), pulmonary arterial wedge pressure (PAWP) ≤15 mmHg (Group I / Nice Clinical Classification of Pulmonary Hypertension) or CTEPH (Group IV / Nice Clinical Classification of Pulmonary Hypertension) defined as inoperable measured at least 3 months after start of full anticoagulation and mPAP \>20 mmHg and PVR ≥2 WU, PAWP ≤15 mmHg; or with persisting or recurrent PH after pulmonary endarterectomy (mPAP \>20 mmHg and PVR ≥2 WU, PAWP ≤15 mmHg measured at least 6 months after surgery (acc. to Simonneau et al. 2018). 3. Treatment naïve patients (with respect to PAH specific medication) and patients pre-treated with an endothelin receptor antagonist or a prostacyclin analogue, pre-treated for 2 months before screening at most (according to upfront combination treatment).\* 4. \*Pre-treated patients need to be stable on endothelin receptor antagonists or prostacyclin treatment for at least two weeks prior to Visit 1. "Stable" is defined as no change in the type of endothelin receptor antagonists or prostacyclin analogue and the respective daily dose. 5. A patient may also be enrolled, if a persisting phosphodiesterase type 5 (PDE-5) inhibitor treatment (pre-treated for 2 months before screening at most) with or without combination treatment with an endothelin receptor antagonist or prostacyclin analogue is to be switched to riociguat by clinical indication, particularly when the patient´s risk-profile remained in intermediate risk group despite adequate initial treatment including PDE5i (defined as at least 3 of the following parameters: clinical signs of progression, persistent WHO-FC III, 6MWD between 165-440m, peak V02 11-15ml/min/kg (35-65% predicted), NTproBNP 300-1400 ng/l, RA-area 18-26cm2,RAP 8-14mmHg, CI 2,0-2,4 l/min) or in case of PDE5i intolerance. Any decision to switch will be made by the clinicians at a regular clinical follow-up visit. 6. Unspecific treatments which may also be used for the treatment of PH such as oral anticoagulants, diuretics, digitalis, calcium channel blockers or oxygen supplementation are permitted. However, treatment with anticoagulants (if indicated) must have been started at least 1 month before visit in patients with PAH 1. 7. RHC results must not be older than 6 months at screening (will be considered as baseline values) and must have been measured in the participating centre under standardized conditions (refer to the study specific Swan Ganz catheterization manual). If the respective measurements have not been performed in context with the patient's regular diagnostic workup, they have to be performed as a part of the study during the pre-study phase (after the patient signed the informed consent). 8. Women without childbearing potential defined as postmenopausal women aged 50 years or older, women with bilateral tubal ligation, women with bilateral ovariectomy, and women with hysterectomy can be included in the study. 9. Women of childbearing potential can only be included in the study if all of the following applies (listed below): a. Negative serum pregnancy test at Screening and a negative urine pregnancy test at study start (visit 1). b. Agreement to undertake monthly urine pregnancy tests during the study and up to at least 30 days after study treatment discontinuation. These tests should be performed by the patient at home. c. Agreement to follow the contraception scheme as specified from Screening until at least 30 days after study treatment discontinuation. 10. Patients who are able to understand and follow instructions and who are able to participate in the study for the entire period. 11. Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures.
Exclusion criteria
1. Pregnant women, or breast-feeding women, or women of childbearing potential not able or willing to comply with study-mandated contraception methods specified above. 2. Patients with PH specific treatment \<2 months before screening. 3. Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study in the opinion of the investigator. 4. Patients with underlying medical disorders with an anticipated life expectancy below 2 years (e.g. active cancer disease with localized and/or metastasized tumour mass). 5. Patients with a history of severe or multiple drug allergies 6. Patients with hypersensitivity to the investigational drug or any of the excipients. 7. Patients unable to perform a valid 6MWD test (e.g. orthopaedic disease, peripheral artery occlusive disease, which affects the patient´s ability to walk). 8. The following specific medications for concomitant treatment of PH or medications which may exert a pharmacodynamic interaction with the study drug are not allowed: 1. Parenteral prostacyclin analogues 2. Specific phosphodiesterase inhibitors (e.g. sildenafil or tadalafil): may be switched to riociguat but not be given in addition to the study drug 3. or unspecific phosphodiesterase inhibitors (e.g. dipyridamole, theophylline) 4. NO donors (e.g. Nitrates) 9. Pulmonary diseases exclusions 1. Moderate to severe bronchial asthma or COPD (Forced Expiratory Volume \<60% predicted) or severe restrictive lung disease (Total Lung Capacity \< 70% predicted) and/or defined as if high resolution computed tomography shows \<20% parenchymal lung disease. 2. Severe congenital abnormalities of the lungs, thorax, and diaphragm. 3. Clinical or radiological evidence of Pulmonary-Veno-Occlusive Disease (PVOD) or Pulmonary Capillary Haemangiomatosis (PCH) or PH and idiopathic interstitial pneumonia (PH-IIP) 10. Cardiovascular exclusions: 1. Uncontrolled arterial hypertension (systolic blood pressure \>180 mmHg and /or diastolic blood pressure \>110 mmHg). 2. Systolic blood pressure \<95 mmHg. 3. Left heart failure with an ejection fraction less than 40%. 4. Pulmonary venous hypertension with pulmonary arterial wedge pressure \>15 mmHg. 5. Hypertrophic obstructive cardiomyopathy. 6. Severe proven or suspected coronary artery disease according to investigators opinion (patients with Canadian Cardiovascular Society Angina Classification class 2-4, and/or requiring nitrates, and/or myocardial infarction within the last 3 months before Visit 1). 7. Clinical evidence of symptomatic atherosclerotic disease (e.g. peripheral artery disease with reduced walking distance, history of stroke with persistent neurological deficit etc). 11. Exclusions related to disorders in organ function: a) Clinically relevant hepatic dysfunction indicated by: i. bilirubin \>2 times upper limit normal ii. and / or hepatic transaminases \>3 times upper limit normal iii. and / or signs of severe hepatic insufficiency (e.g. impaired albumin synthesis with an albumin \< 32 g/l, hepatic encephalopathy \> grade 1a: West Haven Criteria of Altered Mental Status In Hepatic Encephalopathy) b) Renal insufficiency (glomerular filtration rate \<30 ml/min e.g. calculated based on the Cockcroft formula).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in RV (Right Ventricular) Area | Baseline to 24 weeks | echocardiographic analysis right ventricular (RV) area, measured by echocardiography. |
| Change in RA (Right Atrial) Area | Baseline to 24 weeks | echocardiographic analysis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in RV (Right Ventricular) Area | baseline to 12 weeks | echocardiographic analysis |
| Change in RA (Right Atrial) Area | baseline to 12 weeks | echocardiographic analysis |
| Change in Systolic Pulmonary Artery Pressure (sPAP) | baseline to 12 weeks | echocardiographic analysis |
| Change in RV Fractional Area Change (FAC) | baseline to 24 weeks | echocardiographic analysis |
| Change in Peak Velocity of Tricuspid Regurgitation (TRV) | baseline to 12 weeks | echocardiographic analysis |
| Change in Inferior Vena Cava (IVC) Diameter | baseline to 24 weeks | echocardiographic analysis |
| Change in Right Ventricle Outflow Tract Velocity Time Integral (RVOT VTI) | baseline to 12 weeks | echocardiographic analysis |
| Change in Eccentricity Index (EI) | baseline to 24 weeks | Change in left ventricular eccentricity index (LV-EI) from baseline at 24 weeks assessed by echocardiography. LV-EI is the ratio of septical-parallel to septical-perpendicular left ventricular diameters in parasternal short-axis view; normal = 1, increased (≥ 1.1) indicates right ventricular pressure/volume overload |
| Change in Tricuspid Annular Plane Systolic Excursion (TAPSE) | baseline to 12 weeks | echocardiographic analysis |
| Change in Right Ventricular Pump Function (Qualitative) | baseline to 24 weeks | echocardiographic analysis |
| Change in Left Ventricular Pump Function (Qualitative) | baseline to 24 weeks | echocardiographic analysis |
| Change in Left Atrial (LA) Diameter | baseline to 12 weeks | echocardiographic analysis |
| Change in Left Ventricular (LV) Diastolic Function | baseline to 12 weeks | echocardiographic Analysis measured as: (LV transmitral E wave and A wave, E' wave of interventricular septum and lateral wall pulsed tissue Doppler, isovolumic relaxation time, mitral deceleration time) |
| Change in Diameters of Pulmonary Artery (PA) | baseline to 12 weeks | echocardiographic Analysis |
| Change in Cardiac Index (CI) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Cardiac Output (CO) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Systolic Pulmonary Arterial Pressure (sPAP) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Diastolic Pulmonary Arterial Pressure (dPAP) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Mean Pulmonary Arterial Pressure (mPAP) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Pulmonary Arterial Wedge Pressure (PAWP) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Right Atrial Pressure (RAP) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Pulmonary Vascular Resistance (PVR) | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in Central Venous Saturation From Pulmonary Artery | baseline and after 24 weeks | Pulmonary hemodynamics by right heart catheterization |
| Change in 6-minute Walking Distance | baseline to 12 weeks | Change in exercise capacity |
| Forced Vital Capacity (FVC) | baseline to 12 weeks | Change in Lung function Tests |
| Change in Forced Expiratory Volume in One Second (FEV1) | baseline to 12 weeks | Change in Lung function Tests |
| Change in FEV1% of Maximal Vital Capacity (VC Max) | baseline to 12 weeks | Change in Lung function Tests |
| Change in Total Lung Capacity (TLC) | baseline to 12 weeks | Change in Lung function Tests |
| Change in Residual Volume (RV) | baseline to 12 weeks | Change in Lung function Tests |
| Change in Diffusion-limited Carbon Monoxide (DLCO) | baseline to 24 weeks | Change in Lung function Tests |
| Change in DLCO/VA (Krogh) Factor | baseline to 12 weeks | Change in Lung function Tests |
| Change in Partial Pressure of Oxygen (pO2) | baseline to 12 weeks | Change in capillary or arterial blood gas analysis |
| Change in Partial Pressure of Carbon Dioxide (pCO2) | baseline to 12 weeks | Change in capillary or arterial blood gas analysis |
| Change in Oxygen Saturation (SaO2) | baseline to 12 weeks | Change in capillary or arterial blood gas analysis |
| Change in pH | baseline to 24 weeks | Change in capillary or arterial blood gas analysis |
| Change in Blood Pressure | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| Change in Heart Rate | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| Change in Workload | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| Change in Oxygen Consumption as Total (VO2) | baseline to 24 weeks | Change in Cardiopulmonary exercise testing |
| Change in Exhaled Carbon Dioxide (VCO2) | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| Change in Oxygen Saturation (SpO2) | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| Change in Oxygen Pulse | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| Change in Minute Ventilation (VE) | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| Change in Respiratory Equivalents for Oxygen at Rest | baseline to 12 weeks | Change in Cardiopulmonary exercise testing: The respiratory equivalent for oxygen represents the ratio of minute ventilation (VE) to oxygen uptake (VO₂) and reflects the efficiency of ventilation relative to oxygen consumption. |
| Change in Respiratory Equivalents for Carbon Dioxide | baseline to 12 weeks | Change in Cardiopulmonary exercise testing: The respiratory equivalent for carbon dioxide represents the ratio of minute ventilation (VE) to carbon dioxide production (VCO₂) and reflects ventilatory efficiency with respect to carbon dioxide elimination. |
| Change in Respiratory Reserve | baseline to 12 weeks | Change in Cardiopulmonary exercise testing |
| WHO FC | baseline to 12 weeks | Change in WHO functional class |
| NT-proBNP | baseline to 12 weeks | Change in laboratory parameters |
| Haemoglobin Changes | baseline to 12 weeks | Change in laboratory parameters |
| Haematocrit Changes | baseline to 12 weeks | Change in laboratory parameters |
| SGOT/AST Changes | baseline to 12 weeks | Change in liver enzymes |
| SGPT/ALT Changes | baseline to 12 weeks | Change in liver enzymes |
| Bilirubin Changes | baseline to 12 weeks | Change in liver enzymes |
| CRP Changes | baseline to 12 weeks | Change in laboratory parameters |
| Sodium Changes | baseline to 12 weeks | Change in laboratory parameters |
| Urea Changes | baseline to 12 weeks | Change in renal parameters |
| Creatinine Changes | baseline to 12 weeks | Change in renal parameters |
| Creatinine Clearance Changes | baseline to 12 weeks | Change in renal parameters |
| Change in IVC Collapse | baseline to 12 weeks | echocardiographic analysis |
| SF-36: Physical Functioning | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Physical Role Function | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Pain | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: General Health Perception | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Vitality | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Social Functioning | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Emotional Role Function | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Mental Well-being | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Physical Summation Score | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| SF-36: Mental Summation Score | baseline to 24 weeks | Measure Description: Quality of Life (QoL) was assessed using the SF 36-questionnaire. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale, i.e. a score of 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability. Sections: vitality; physical functioning; bodily pain; general health perceptions; physical role functioning; emotional role functioning; social role functioning; mental health. Two summation scores, physical and mental summation score, were calculated. |
| Change in Oxygen Consumption Per kg Body Weight (VO2/kg) | Baseline to 24 weeks | Change in Cardiopulmonary Exercise testing |
Countries
Germany
Contacts
PRINCIPAL_INVESTIGATOREkkehard HD Grünig, MD
Thoraxklinik at the University of Heidelberg
Participant flow
Recruitment details
Participants were recruited between April 2022 and May 2025. The first participant was enrolled on 13 April 2022, the last on 30 May 2025.
Pre-assignment details
Overall, 30 patients were enrolled and commenced study treatment.
Baseline characteristics
| Characteristic | — |
|---|---|
| 6 Minute walking distance: Borg dyspnea score | 4.00 scores on a scale STANDARD_DEVIATION 3.05 |
| 6 Minute walking distance: Distance | 359.83 m STANDARD_DEVIATION 123.01 |
| 6 Minute walking distance: Oxygen saturation at test end | 87.17 percent STANDARD_DEVIATION 8.69 |
| Age, Continuous | 61.23 years STANDARD_DEVIATION 14.52 |
| Blood gas analysis: Base excess | -1.14 mmol/l STANDARD_DEVIATION 2.77 |
| Blood gas analysis: Bicarbonates | 22.54 mmol/l STANDARD_DEVIATION 3.09 |
| Blood gas analysis: Oxygen saturation (SaO2) | 94.14 percent STANDARD_DEVIATION 2.56 |
| Blood gas analysis: Partial pressure of carbon dioxide (PaCO2) | 33.99 mmHg STANDARD_DEVIATION 4.75 |
| Blood gas analysis: Partial pressure of oxygen (PaO2) | 69.00 mmHg STANDARD_DEVIATION 10.71 |
| Blood gas analysis: pH | 7.43 pH STANDARD_DEVIATION 0.04 |
| Concomitant diseases Adipositas | 5 Participants |
| Concomitant diseases Arrythmias | 4 Participants |
| Concomitant diseases Asthma | 3 Participants |
| Concomitant diseases Bronchiectasis | 1 Participants |
| Concomitant diseases Depression | 1 Participants |
| Concomitant diseases Diabetes mellitus | 7 Participants |
| Concomitant diseases Diverticulosis | 1 Participants |
| Concomitant diseases Dyslipidemia | 8 Participants |
| Concomitant diseases Gastritis | 2 Participants |
| Concomitant diseases Gout | 2 Participants |
| Concomitant diseases Heart block | 4 Participants |
| Concomitant diseases Hepatic coagulation disorder | 1 Participants |
| Concomitant diseases HFpEF | 1 Participants |
| Concomitant diseases Hypacusis | 1 Participants |
| Concomitant diseases Hyperuricemia | 4 Participants |
| Concomitant diseases Hypoxemia | 13 Participants |
| Concomitant diseases Iron deficiency | 7 Participants |
| Concomitant diseases Liver fibrom | 1 Participants |
| Concomitant diseases Mild COPD | 11 Participants |
| Concomitant diseases Mild restrictive lung disease | 4 Participants |
| Concomitant diseases Nasal hyperplasia | 1 Participants |
| Concomitant diseases Obstructive sleep apnea syndrome | 3 Participants |
| Concomitant diseases Past infections (any) | 8 Participants |
| Concomitant diseases Peripheral arterial occlusive disease | 2 Participants |
| Concomitant diseases Portal hypertension | 1 Participants |
| Concomitant diseases Prostate hyperplasia | 2 Participants |
| Concomitant diseases Pulmonary embolism | 4 Participants |
| Concomitant diseases Scoliosis | 1 Participants |
| Concomitant diseases Seminoma | 1 Participants |
| Concomitant diseases Sinusitis | 2 Participants |
| Concomitant diseases Sinus osteoma | 1 Participants |
| Concomitant diseases State after Appendectomy | 4 Participants |
| Concomitant diseases State after Cholezystectomy | 2 Participants |
| Concomitant diseases Steirlisation | 2 Participants |
| Concomitant diseases Thyroid dysfunction | 5 Participants |
| Concomitant diseases Tonsillectomy | 3 Participants |
| Concomitant diseases Total endoprothesis | 2 Participants |
| Concomitant diseases Treated arterial hypertension | 16 Participants |
| Concomitant diseases Treated coronary heart disease | 14 Participants |
| Concomitant diseases Ureterolithiasis | 1 Participants |
| Concomitant diseases Varicosis | 2 Participants |
| Concomitant diseases Vitamin D deficiency | 2 Participants |
| CPET: Diastolic blood pressure Diastolic blood pressure at anaerobic threshold | 86.91 mmHg STANDARD_DEVIATION 8.98 |
| CPET: Diastolic blood pressure Diastolic blood pressure at peak workload | 84.67 mmHg STANDARD_DEVIATION 12.95 |
| CPET: Diastolic blood pressure Diastolic blood pressure at rest | 72.42 mmHg STANDARD_DEVIATION 6.02 |
| CPET: Equivalents for O2 at rest | 40.50 ratio STANDARD_DEVIATION 0.71 |
| CPET: Heart rate Heart rate at anaerobic threshold | 104.82 beats/min STANDARD_DEVIATION 17.3 |
| CPET: Heart rate Heart rate at peak workload | 124.17 beats/min STANDARD_DEVIATION 18.86 |
| CPET: Heart rate Heart rate at rest | 74.75 beats/min STANDARD_DEVIATION 9.17 |
| CPET: Minute Ventilation (VE) VE at anaerobic threshold | 38.36 L/min STANDARD_DEVIATION 15.28 |
| CPET: Minute Ventilation (VE) VE at peak workload | 57.75 L/min STANDARD_DEVIATION 15.97 |
| CPET: Minute Ventilation (VE) VE at rest | 15.33 L/min STANDARD_DEVIATION 6.39 |
| CPET: O2-pulse O2-pulse at anaerobic threshold | 8.71 ml STANDARD_DEVIATION 3.19 |
| CPET: O2-pulse O2-pulse at peak workload | 9.52 ml STANDARD_DEVIATION 3.19 |
| CPET: O2-pulse O2-pulse at rest | 4.91 ml STANDARD_DEVIATION 1.77 |
| CPET: Oxygen saturation (SpO2) SpO2 at anaerobic threshold | 92.00 percent STANDARD_DEVIATION 6.97 |
| CPET: Oxygen saturation (SpO2) SpO2 at peak workload | 90.67 percent STANDARD_DEVIATION 8.12 |
| CPET: Oxygen saturation (SpO2) SpO2 at rest | 97.00 percent STANDARD_DEVIATION 2 |
| CPET: Respiratory reserve Respiratory reserve at anaerobic threshold | 41.50 percent STANDARD_DEVIATION 21.76 |
| CPET: Respiratory reserve Respiratory reserve at peak workload | 40.55 percent STANDARD_DEVIATION 13.19 |
| CPET: Respiratory reserve Respiratory reserve at rest | 52.75 percent STANDARD_DEVIATION 44.18 |
| CPET: Systolic blood pressure Systolic blood pressure at anaerobic threshold | 145.73 mmHg STANDARD_DEVIATION 16.64 |
| CPET: Systolic blood pressure Systolic blood pressure at peak workload | 151.83 mmHg STANDARD_DEVIATION 16.79 |
| CPET: Systolic blood pressure Systolic blood pressure at rest | 115.33 mmHg STANDARD_DEVIATION 9.62 |
| CPET: Volume of exhaled carbondioxide (VCO2) VCO2 at anaerobic threshold | 886.82 ml/min STANDARD_DEVIATION 483.67 |
| CPET: Volume of exhaled carbondioxide (VCO2) VCO2 at peak workload | 1353.58 ml/min STANDARD_DEVIATION 519.86 |
| CPET: Volume of exhaled carbondioxide (VCO2) VCO2 at rest | 329.17 ml/min STANDARD_DEVIATION 125.58 |
| CPET: Volume of Oxygen consumption per kg of bodyweight (VO2/kg) VO2/kg at anaerobic threshold | 10.66 ml/min/kg STANDARD_DEVIATION 4.14 |
| CPET: Volume of Oxygen consumption per kg of bodyweight (VO2/kg) VO2/kg at peak workload | 14.24 ml/min/kg STANDARD_DEVIATION 4.22 |
| CPET: Volume of Oxygen consumption per kg of bodyweight (VO2/kg) VO2/kg at rest | 4.38 ml/min/kg STANDARD_DEVIATION 1.03 |
| CPET: Volume of oxygen consumption (VO2) in total VO2 at anaerobic threshold | 909.45 ml/min STANDARD_DEVIATION 390.23 |
| CPET: Volume of oxygen consumption (VO2) in total VO2 at peak workload | 1180.75 ml/min STANDARD_DEVIATION 427.69 |
| CPET: Volume of oxygen consumption (VO2) in total VO2 at rest | 362.33 ml/min STANDARD_DEVIATION 125.05 |
| CPET: workload Peak workload | 95.83 watt STANDARD_DEVIATION 45.02 |
| CPET: workload Workload at anaerobic threshold | 65.91 watt STANDARD_DEVIATION 34.05 |
| Duration of Pulmonary hypertension (PH) | 3.59 years STANDARD_DEVIATION 6.98 |
| Echocardiography at rest: Diameter of pulmonary artery (PA) | 2.96 cm STANDARD_DEVIATION 0.75 |
| Echocardiography at rest: estimated systolic pulmonary arterial pressure (sPAP) | 57.83 mmHg STANDARD_DEVIATION 17.04 |
| Echocardiography at rest: Fractional area change (FAC) | 16.96 percent STANDARD_DEVIATION 5.18 |
| Echocardiography at rest: Inferior vena cava (IVC) collapse | 53.19 % STANDARD_DEVIATION 23.08 |
| Echocardiography at rest: Inferior vena cava (IVC) diameter | 1.64 cm STANDARD_DEVIATION 0.46 |
| Echocardiography at rest: Left atrial (LA) diameter | 3.27 cm STANDARD_DEVIATION 0.53 |
| Echocardiography at rest: Left ventricular diastolic dysfunction No | 15 Participants |
| Echocardiography at rest: Left ventricular diastolic dysfunction Yes | 15 Participants |
| Echocardiography at rest: Left ventricular eccentricity index (LV-EI) | 1.32 index STANDARD_DEVIATION 0.24 |
| Echocardiography at rest: Qualitative assesment of left ventricular pump function mild impairment | 1 Participants |
| Echocardiography at rest: Qualitative assesment of left ventricular pump function moderate impairment | 0 Participants |
| Echocardiography at rest: Qualitative assesment of left ventricular pump function normal/good | 29 Participants |
| Echocardiography at rest: Qualitative assesment of left ventricular pump function severe impairment | 0 Participants |
| Echocardiography at rest: Qualitative assesment of right ventricular pump function mild impairment | 3 Participants |
| Echocardiography at rest: Qualitative assesment of right ventricular pump function moderate impairment | 6 Participants |
| Echocardiography at rest: Qualitative assesment of right ventricular pump function normal/good | 1 Participants |
| Echocardiography at rest: Qualitative assesment of right ventricular pump function severe impairment | 20 Participants |
| Echocardiography at rest: Right atrial (RA) area | 22.50 cm^2 STANDARD_DEVIATION 6.14 |
| Echocardiography at rest: Right ventricular (RV) area | 26.10 cm^2 STANDARD_DEVIATION 5.5 |
| Echocardiography at rest: Tricuspid annular plane systolic excursion (TAPSE) | 2.15 cm STANDARD_DEVIATION 0.42 |
| Height | 176.37 cm STANDARD_DEVIATION 9.43 |
| Hemodynamics at rest: Cardiac index (CI) | 2.62 l/min/m^2 STANDARD_DEVIATION 0.74 |
| Hemodynamics at rest: Cardiac output (CO) | 5.25 l/min STANDARD_DEVIATION 1.56 |
| Hemodynamics at rest: diastolic pulmonary arterial pressure (dPAP) | 25.53 mmHg STANDARD_DEVIATION 6.02 |
| Hemodynamics at rest: mean pulmonary arterial pressure (mPAP) | 40.97 mmHg STANDARD_DEVIATION 9.44 |
| Hemodynamics at rest: Pulmonary arterial wedge pressure (PAWP) | 9.07 mmHg STANDARD_DEVIATION 3.06 |
| Hemodynamics at rest: Pulmonary vascular resistance (PVR) | 6.72 WU STANDARD_DEVIATION 3.47 |
| Hemodynamics at rest: Right atrial pressure (RAP) | 6.13 mmHg STANDARD_DEVIATION 3.33 |
| Hemodynamics at rest: systolic pulmonary arterial pressure (sPAP) | 68.10 mmHg STANDARD_DEVIATION 19.73 |
| Hemodynamics at rest: Venous oxygen saturation (SvO2) | 70.47 percent STANDARD_DEVIATION 6.98 |
| Laboratory: Bilirubin | 0.82 mg/dl STANDARD_DEVIATION 0.51 |
| Laboratory: Creatinine | 1.05 mg/dl STANDARD_DEVIATION 0.24 |
| Laboratory: CRP | 5.00 mg/l STANDARD_DEVIATION 7.03 |
| Laboratory: Hematocrit | 0.46 STANDARD_DEVIATION 0.06 |
| Laboratory: Hemoglobin | 15.48 g/dl STANDARD_DEVIATION 2.23 |
| Laboratory: NTproBNP | 1555.04 ng/l STANDARD_DEVIATION 3165.73 |
| Laboratory: SGOT | 27.43 U/l STANDARD_DEVIATION 22.46 |
| Laboratory: SGPT | 29.50 U/l STANDARD_DEVIATION 33.63 |
| Laboratory: Sodium | 140.39 mmol/l STANDARD_DEVIATION 1.83 |
| Laboratory: Urea | 38.14 mg/dl STANDARD_DEVIATION 18.4 |
| Laboratory: Uric acid | 6.71 mg/dl STANDARD_DEVIATION 2.17 |
| Lung function: Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | 51.64 %predicted STANDARD_DEVIATION 21.53 |
| Lung function: Diffusion Capacity corrected for Alveolar Volume (DLCO/VA) | 59.92 %predicted STANDARD_DEVIATION 23.33 |
| Lung function: Forced expiratory volume in 1 second (FEV1) | 81.95 %predicted STANDARD_DEVIATION 11.85 |
| Lung function: Forced vital capacity (FVC) | 84.54 %predicted STANDARD_DEVIATION 11.37 |
| Lung function: Residual volume (RV) | 99.29 %predicted STANDARD_DEVIATION 26.4 |
| Lung function: Total lung capacity (TLC) | 91.04 %(predicted) STANDARD_DEVIATION 12.54 |
| PAH Etiology Connective tissue diseases | 1 Participants |
| PAH Etiology Drug- and toxin-induced PAH | 1 Participants |
| PAH Etiology Heritable | 4 Participants |
| PAH Etiology Idiopathic | 18 Participants |
| PAH Etiology PAH with comorbiditis | 5 Participants |
| PAH Etiology Portal hypertension | 1 Participants |
| Physical summation score | 58.17 scores on a scale STANDARD_DEVIATION 19.65 |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 23 Participants |
| Short Form-36 Heath Survey: Emotional role function | 75.86 scores on a scale STANDARD_DEVIATION 37.72 |
| Short Form-36 Heath Survey: General health perception | 50.76 scores on a scale STANDARD_DEVIATION 19.74 |
| Short Form-36 Heath Survey: Mental summation score | 65.14 scores on a scale STANDARD_DEVIATION 18.19 |
| Short Form-36 Heath Survey: Mental well-being | 70.76 scores on a scale STANDARD_DEVIATION 19.22 |
| Short Form-36 Heath Survey: Pain | 85.83 scores on a scale STANDARD_DEVIATION 19.79 |
| Short Form-36 Heath Survey: Physical functioning | 54.14 scores on a scale STANDARD_DEVIATION 26.99 |
| Short Form-36 Heath Survey: Physical role functioning | 49.14 scores on a scale STANDARD_DEVIATION 45.55 |
| Short Form-36 Heath Survey: Social functioning | 76.90 scores on a scale STANDARD_DEVIATION 23.31 |
| Short Form-36 Heath Survey: Vitality | 51.90 scores on a scale STANDARD_DEVIATION 18.15 |
| Vital signs: Diastolic blood pressure | 72.03 mmHg STANDARD_DEVIATION 12.13 |
| Vital signs: Heart rate | 73.17 beats/min STANDARD_DEVIATION 12.73 |
| Vital signs: Oxygen saturation (SpO2) | 94.79 percent STANDARD_DEVIATION 2.9 |
| Vital signs: Systolic blood pressure | 120.43 mmHg STANDARD_DEVIATION 13.94 |
| Weight | 81.97 kg STANDARD_DEVIATION 12.49 |
| WHO Functional Class I | 0 Participants |
| WHO Functional Class II | 2 Participants |
| WHO Functional Class III | 25 Participants |
| WHO Functional Class IV | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 29 / 30 |
| serious Total, serious adverse events | 3 / 30 |
Outcome results
None listed