Non-operable Chronic Thromboembolic Pulmonary Hypertension
Conditions
Brief summary
The primary purpose of this study is to determine the effect on six-minute walking test (6MWT) distance after 24 weeks treatment with subcutaneous (SC) Treprostinil Sodium in patients with Severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension.
Detailed description
Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by non-resolving organized thromboembolic obstructing the pulmonary vascular bed. These thrombi are resistant to thrombolytic therapy and chronic plasmatic anticoagulation. An increase in pulmonary vascular resistance (PVR), right ventricular overload, and eventually right ventricular failure ensue. The treatment of choice for CTEPH is pulmonary endarterectomy (PEA), providing a potential cure for the disease. However, about 50 % of patients are not candidates for surgery, mainly because of distal location of thromboemboli. Despite recent advances in the treatment of pulmonary arterial hypertension (PAH), medical treatments have not been recommended for inoperable CTEPH, because of the concept that a predominantly major vessel obstructive arteriopathy would not be suitable for vasodilators. Furthermore, a major drawback of i.v. prostacyclin therapy is the need for a permanent central venous access that increases the risk of infection (0.22-0.68 per patient per year), thrombosis and new major vessel thromboembolism.
Interventions
Sponsors
SciPharm SàRL
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Subject must be competent to understand the information given in the written informed consent and from the investigator and must sign and date the informed consent prior to any study mandated procedure. 2. Subject must be at least 18 years of age and can be of any ethnical origin 3. Women of child bearing potential must be surgically sterile or postmenopausal (amenorrhea for at least 12 months) or using an acceptable form of contraception. Reliable contraception is defined as a method which results in a low failure rate, i.e., less than 1% per year when used correctly such as, implants, injectables, oral contraceptive medications, sexual abstinence, or a vasectomised partner. 4. Subject must have a current diagnosis of CTEPH, as defined by the following criteria: * A test result of perfusion scintigraphy and pulmonary angiography and/or multislice CT not older than 6 months, consistent with the diagnosis CTEPH. In case of recurrent PH after PEA, test results from before the surgery are acceptable if a typical specimen was harvested during PEA substantiating the diagnosis of CTEPH. * A right heart catheterization, not older than 6 months, consistent with the diagnosis CTEPH but specifically with a mean pulmonary artery pressure (PAPm) of \> 25 mmHg, and a PVR of \> 300 dyn.s.cm-5 * At least three months of effective anticoagulation therapy (without improvement / to exclude subacute pulmonary emboli) 5. Subject must have CTEPH classified as severe, as defined by the following criteria: * An un-encouraged 6MWT distance of between 150 and 400 meters * Classification in the WHO/New York Heart Association (NYHA) functional class III or IV 6. The subject must not be suitable to undergo a PEA and is therefore defined as non-operable, due to at least one of the following reasons: * Clot is not accessible * Discrepancy between severity of PH and morphologic lesion * Subject is not a good surgical candidate for other reasons: PVR \> 1500 dynes.s.cm-5 Age Comorbidity No functional lung parenchyma * Unsuccessful PEA in the past with residual/recurrent CTEPH * No consent for PEA given by subject 7. Subject must be willing and able to follow all study procedures Exclusion: 1. Subject with any form of pulmonary arterial hypertension or any disease known to cause PAH (WHO Group I) 2. Subjects with a total lung capacity (TLC) of \< 70% predicted or a forced expiratory volume/forced vital capacity (FEV1/FVC \< 50%) 3. Subject who received any prostanoids, within the 30 days before screening or be scheduled to receive prostanoids during the course of the study 4. Subject with a new type of chronic therapy (a different category of vasodilator or diuretic) for PAH added within the last month, except anticoagulants 5. Subject with an increased risk for hemorrhage or stroke or with a major cardiovascular event during the past 6 months. 6. Unstable subjects for any reason (according to the investigators discretion) 7. Subject who received any investigational medication within 30 days prior to the screening visit of this study or be scheduled to receive another investigational drug during the course of this study 8. Subject with a known intolerance to any drug relevant for this trial, especially to Treprostinil sodium or prostanoids 9. Subject with a history or suspicion of non compliance 10. Subject who has any musculoskeletal disease or any other disease that would limit ambulation 11. Subject with other cardiovascular, liver, renal, hematologic, gastrointestinal immunologic, endocrine, metabolic, or central nervous system disease that, in the opinion of the investigator, may adversely affect the safety of the subject and /or efficacy of the study drug or limit the lifespan of the subject 12. Female who is considering pregnancy or who is pregnant and/or lactating 13. Subject who is an investigator or any other team member involved directly or indirectly in the conduct of the clinical study. 14. Subject who is an inmate of a psychiatric ward, prison or is suspected not to be able to give consent of his free will
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 6-minute Walk Test Distance After 24 Weeks | Baseline and 24 weeks | To determine the effect of subcutaneous Treprostinil sodium on 6-minute walk test distance after 24 weeks in patients with severe non-operable chronic thromboembolic pulmonary hypertension severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension Time frame of the 6-minute walk test: The 6-minute walk test was conducted at the following visits: * baseline (day 1) * Visit 6 (day 168) In case of missing values, Last-Observation-Carried-Forward imputation method was used. In such cases values documented at Visit 4 (day84) were used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect on Maximal Borg Score During 6-minutes Walk Test | Baseline and 24 weeks | The Borg scale was used for rating of dyspnea during 6-minutes walk test. The scale is defined from 0 to \> 10 (upper bound) (0 = NOTHING AT ALL; 0.5 = VERY VERY SLIGHT (just noticeable); 1 = VERY SLIGHT; 2 = SLIGHT; 3 = MODERATE; 4 = SOMEWHAT SEVERE; 5 = SEVERE; 6-9 = VERY SEVERE; 10 = VERY VERY SEVERE (almost maximum); \>10 MAXIMUM). As can be seen with the scale, the higher scale values represent a worse outcome. As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 48 patients in low dose group. |
| Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | Baseline and 24 weeks | Class I - Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope. Class II - Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class III - Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope Class IV - Patients with pulmonary hypertension in the inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. |
| Effect on Quality of Life by the MINNESOTA Questionnaire | Baseline and 24 weeks | This questionnaire is composed of 21 questions relating to limitations in lifestyle associated with Heart Failure. Respondents use a 5-point scale that ranges from 0 (none) to 5 (too much), with a score of 0 representing no limitation and a score of 5 representing maximum limitation. The change in individual score sum was evaluated and is displayed in the results, with a possible range of 0-105. Higher values indicate more limitations in Quality of Life. As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 50 patients randomized to high dose group and 46 patients in low dose group. |
| Effect on N-terminal Pro-BNP Levels | Baseline and 24 weeks | baseline values, assessment after 12 and 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 46 patients randomized to high dose group and 46 patients in low dose group. |
| Effect on Hemodynamic Parameter (PVR - Pulmonary Vascular Resistance) | Baseline and 24 weeks | baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group. |
| Number of Participants With Clinical Worsening | 12 weeks and 24 weeks | Clinical worsening defined as a decrease of 6-minute walk test distance of more than 20% from baseline due to Chronic Thromboembolic Pulmonary Hypertension, decrease of New York Heart Association functional class, hospitalization with the requirement for additional Pulmonary Hypertension specific treatment and/or death due to worsening Chronic Thromboembolic Pulmonary Hypertension. Clinical Worsening was assessed after 12 weeks and 24 weeks, participants experiencing clinical worsening at any time-point are reported. |
| Effect on Hemodynamic Parameter (CO - Cardiac Output) | Baseline and 24 weeks | baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group. |
| Effect on Hemodynamic Parameter (mPAP - Mean Pulmonary Arterial Pressure) | Baseline and 24 weeks | baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 47 patients randomized to high dose group and 47 patients in low dose group. |
| Effect on Hemodynamic Parameter (mRap - Mean Right Atrial Pressure) | Baseline and 24 weeks | baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group. |
| Effect on Signs & Symptoms of the CTEPH | Baseline and 24 weeks | baseline values, assessment after 24 weeks |
| Effect on Hemodynamic Parameter (CI - Cardiac Index) | Baseline and 24 weeks | baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group. |
Countries
Austria, Czechia, Germany, Poland
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| High Dose Treprostinil sodium high dose | 53 |
| Low Dose Treprostinil sodium low dose | 52 |
| Total | 105 |
Baseline characteristics
| Characteristic | High Dose | Low Dose | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 38 Participants | 25 Participants | 63 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 26 Participants | 41 Participants |
| Age, Continuous | 68.06 years STANDARD_DEVIATION 11.16 | 60.58 years STANDARD_DEVIATION 14.59 | 64.35 years STANDARD_DEVIATION 13.44 |
| Region of Enrollment Austria | 28 participants | 26 participants | 54 participants |
| Region of Enrollment Czechia | 17 participants | 17 participants | 34 participants |
| Region of Enrollment Germany | 0 participants | 1 participants | 1 participants |
| Region of Enrollment Poland | 8 participants | 8 participants | 16 participants |
| Sex: Female, Male Female | 19 Participants | 30 Participants | 49 Participants |
| Sex: Female, Male Male | 34 Participants | 22 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 53 | 1 / 52 |
| other Total, other adverse events | 53 / 53 | 51 / 52 |
| serious Total, serious adverse events | 9 / 53 | 10 / 52 |
Outcome results
Primary
Change in 6-minute Walk Test Distance After 24 Weeks
To determine the effect of subcutaneous Treprostinil sodium on 6-minute walk test distance after 24 weeks in patients with severe non-operable chronic thromboembolic pulmonary hypertension severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension Time frame of the 6-minute walk test: The 6-minute walk test was conducted at the following visits: * baseline (day 1) * Visit 6 (day 168) In case of missing values, Last-Observation-Carried-Forward imputation method was used. In such cases values documented at Visit 4 (day84) were used.
Time frame: Baseline and 24 weeks
Population: All randomized subjects who received at least one dose of study medication.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Change in 6-minute Walk Test Distance After 24 Weeks | 45.43 m | Standard Deviation 71.29 |
| Low Dose | Change in 6-minute Walk Test Distance After 24 Weeks | 3.83 m | Standard Deviation 56.21 |
p-value: 0.002ANCOVA
p-value: 0.0003Wilcoxon (Mann-Whitney)
Secondary
Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class
Class I - Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope. Class II - Patients with pulmonary hypertension resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class III - Patients with pulmonary hypertension resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes undue dyspnea or fatigue, chest pain or near syncope Class IV - Patients with pulmonary hypertension in the inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity.
Time frame: Baseline and 24 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| High Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | Improved | 27 Participants |
| High Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | No change | 22 Participants |
| High Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | Worse | 2 Participants |
| High Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | Not done | 2 Participants |
| Low Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | Not done | 4 Participants |
| Low Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | Improved | 9 Participants |
| Low Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | Worse | 3 Participants |
| Low Dose | Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class | No change | 36 Participants |
p-value: 0.0019Chi-squared
Secondary
Effect on Hemodynamic Parameter (CI - Cardiac Index)
baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on Hemodynamic Parameter (CI - Cardiac Index) | 0.42 L/min/m2 | Standard Deviation 0.9 |
| Low Dose | Effect on Hemodynamic Parameter (CI - Cardiac Index) | -0.16 L/min/m2 | Standard Deviation 0.54 |
p-value: 0.000003Wilcoxon (Mann-Whitney)
Secondary
Effect on Hemodynamic Parameter (CO - Cardiac Output)
baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on Hemodynamic Parameter (CO - Cardiac Output) | 0.63 L/min | Standard Deviation 1.47 |
| Low Dose | Effect on Hemodynamic Parameter (CO - Cardiac Output) | -0.22 L/min | Standard Deviation 1.06 |
p-value: 0.00008Wilcoxon (Mann-Whitney)
Secondary
Effect on Hemodynamic Parameter (mPAP - Mean Pulmonary Arterial Pressure)
baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 47 patients randomized to high dose group and 47 patients in low dose group.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on Hemodynamic Parameter (mPAP - Mean Pulmonary Arterial Pressure) | -3.36 mmHg | Standard Deviation 8.04 |
| Low Dose | Effect on Hemodynamic Parameter (mPAP - Mean Pulmonary Arterial Pressure) | -0.4 mmHg | Standard Deviation 6.87 |
p-value: 0.04Wilcoxon (Mann-Whitney)
Secondary
Effect on Hemodynamic Parameter (mRap - Mean Right Atrial Pressure)
baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on Hemodynamic Parameter (mRap - Mean Right Atrial Pressure) | 0.65 mmHg | Standard Deviation 5.08 |
| Low Dose | Effect on Hemodynamic Parameter (mRap - Mean Right Atrial Pressure) | 2.87 mmHg | Standard Deviation 6.82 |
p-value: 0.227Wilcoxon (Mann-Whitney)
Secondary
Effect on Hemodynamic Parameter (PVR - Pulmonary Vascular Resistance)
baseline values, assessment after 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 47 patients in low dose group.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on Hemodynamic Parameter (PVR - Pulmonary Vascular Resistance) | -214.23 dyn.s.cm^-5 | Standard Deviation 324.28 |
| Low Dose | Effect on Hemodynamic Parameter (PVR - Pulmonary Vascular Resistance) | 72.96 dyn.s.cm^-5 | Standard Deviation 284.95 |
p-value: 0.00001Wilcoxon (Mann-Whitney)
Secondary
Effect on Maximal Borg Score During 6-minutes Walk Test
The Borg scale was used for rating of dyspnea during 6-minutes walk test. The scale is defined from 0 to \> 10 (upper bound) (0 = NOTHING AT ALL; 0.5 = VERY VERY SLIGHT (just noticeable); 1 = VERY SLIGHT; 2 = SLIGHT; 3 = MODERATE; 4 = SOMEWHAT SEVERE; 5 = SEVERE; 6-9 = VERY SEVERE; 10 = VERY VERY SEVERE (almost maximum); \>10 MAXIMUM). As can be seen with the scale, the higher scale values represent a worse outcome. As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 48 patients randomized to high dose group and 48 patients in low dose group.
Time frame: Baseline and 24 weeks
Population: For this endpoint no imputation role was applied. For 48 patients of the high dose group, as well as for the low dose group, baseline data and also 24 week data are available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on Maximal Borg Score During 6-minutes Walk Test | -0.44 units on a scale | Standard Deviation 2.21 |
| Low Dose | Effect on Maximal Borg Score During 6-minutes Walk Test | -0.13 units on a scale | Standard Deviation 2.43 |
p-value: 0.307Wilcoxon (Mann-Whitney)
Secondary
Effect on N-terminal Pro-BNP Levels
baseline values, assessment after 12 and 24 weeks As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 46 patients randomized to high dose group and 46 patients in low dose group.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on N-terminal Pro-BNP Levels | 0.84 percentage change to baseline | Standard Deviation 63.32 |
| Low Dose | Effect on N-terminal Pro-BNP Levels | 41.68 percentage change to baseline | Standard Deviation 104.2 |
p-value: 0.032Wilcoxon (Mann-Whitney)
Secondary
Effect on Quality of Life by the MINNESOTA Questionnaire
This questionnaire is composed of 21 questions relating to limitations in lifestyle associated with Heart Failure. Respondents use a 5-point scale that ranges from 0 (none) to 5 (too much), with a score of 0 representing no limitation and a score of 5 representing maximum limitation. The change in individual score sum was evaluated and is displayed in the results, with a possible range of 0-105. Higher values indicate more limitations in Quality of Life. As no imputation rule applied only full-data sets were evaluated. Complete data sets were available for 50 patients randomized to high dose group and 46 patients in low dose group.
Time frame: Baseline and 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| High Dose | Effect on Quality of Life by the MINNESOTA Questionnaire | -6.36 units on a scale | Standard Deviation 22.9 |
| Low Dose | Effect on Quality of Life by the MINNESOTA Questionnaire | -4.63 units on a scale | Standard Deviation 19.34 |
p-value: 0.557Wilcoxon (Mann-Whitney)
Secondary
Effect on Signs & Symptoms of the CTEPH
baseline values, assessment after 24 weeks
Time frame: Baseline and 24 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| High Dose | Effect on Signs & Symptoms of the CTEPH | Orthopnoea : Baseline | 9 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea at rest : Baseline | 7 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Nausea/Vomiting : Baseline | 4 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea at rest : Week 24 | 3 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Orthopnoea : Week 24 | 3 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Paroxysmal nocturnal dyspnoea : Baseline | 7 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Ascites : Baseline | 2 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Paroxysmal nocturnal dyspnoea : Week 24 | 4 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Chest pain : Baseline | 13 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea on exertion : Baseline | 53 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Dizziness : Baseline | 25 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea on exertion : Week 24 | 46 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Ascites : Week 24 | 1 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Syncope : Baseline | 3 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Dizziness : Week 24 | 11 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Syncope : Week 24 | 1 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Chest pain : Week 24 | 8 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Fatigue : Baseline | 33 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Palpitations : Baseline | 19 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Fatigue : Week 24 | 26 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Nausea/Vomiting : Week 24 | 5 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Thirst : Baseline | 12 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Palpitations : Week 24 | 9 participants |
| High Dose | Effect on Signs & Symptoms of the CTEPH | Thirst : Week 24 | 12 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Paroxysmal nocturnal dyspnoea : Baseline | 1 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Thirst : Week 24 | 13 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Ascites : Baseline | 3 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Ascites : Week 24 | 3 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Nausea/Vomiting : Baseline | 9 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Nausea/Vomiting : Week 24 | 9 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Chest pain : Baseline | 11 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Chest pain : Week 24 | 3 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Orthopnoea : Baseline | 9 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Orthopnoea : Week 24 | 5 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Dizziness : Baseline | 21 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Dizziness : Week 24 | 10 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Palpitations : Baseline | 18 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Palpitations : Week 24 | 11 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea at rest : Baseline | 10 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea at rest : Week 24 | 10 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Paroxysmal nocturnal dyspnoea : Week 24 | 3 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea on exertion : Baseline | 51 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Dyspnoea on exertion : Week 24 | 43 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Syncope : Baseline | 6 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Syncope : Week 24 | 2 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Fatigue : Baseline | 37 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Fatigue : Week 24 | 27 participants |
| Low Dose | Effect on Signs & Symptoms of the CTEPH | Thirst : Baseline | 21 participants |
Secondary
Number of Participants With Clinical Worsening
Clinical worsening defined as a decrease of 6-minute walk test distance of more than 20% from baseline due to Chronic Thromboembolic Pulmonary Hypertension, decrease of New York Heart Association functional class, hospitalization with the requirement for additional Pulmonary Hypertension specific treatment and/or death due to worsening Chronic Thromboembolic Pulmonary Hypertension. Clinical Worsening was assessed after 12 weeks and 24 weeks, participants experiencing clinical worsening at any time-point are reported.
Time frame: 12 weeks and 24 weeks
Population: All randomized subjects who received at least one dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| High Dose | Number of Participants With Clinical Worsening | 7 Participants |
| Low Dose | Number of Participants With Clinical Worsening | 12 Participants |
p-value: 0.605Wilcoxon (Mann-Whitney)