Patients with Severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension
Conditions
Interventions
Product Name: Treprostinil Sodium
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Treprostinil
CAS Number: 289480644
Other descriptive name: TREPROSTINIL SODIUM
Concentration unit: mg/
Sponsors
SCIPHARM SáRL
Eligibility
Sex/Gender
All
Inclusion criteria
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 could 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 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 a CTEPH classified as severe, as defined by the following criteria: • An un-encouraged 6MWT of between 150 and 400 meters • Classification in the WHO/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 the patient 7. Subject must be willing and able to follow all study procedures Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 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 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 study especially to Treprostinil sodium or prostanoids 9. Subject with a history or suspicion of non compliance 10. Have 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 |
|---|---|
| Main Objective: To determine the effect of subcutaneous Treprostinil sodium on 6MWT distance after 24 weeks in patients with severe non-operable chronic thromboembolic pulmonary hypertension;Secondary Objective: 1. To assess clinical worsening defined as a decrease of 6MWT distance of more than 20% from baseline due to CTEPH, as decrease of NYHA functional class, hospitalization with the requirement for additional PH specific treatment and/or death due to worsening CTEPH 2. To assess the effect on maximal Borg score, heart rate and oxygen saturation during 6MWT 3. To assess the effect on WHO NYHA functional class 4. To assess the effect on QOL by the MINNESOTA instrument Exploratory analyses: 1. To assess the effect on pro-BNP levels 2. To assess the effect on hemodynamic parameters 3. To assess the effect on signs & symptoms;Primary end point(s): Change in 6MWT distance after 24 weeks;Timepoint(s) of evaluation of this end point: Baseline, Visit 4 (week 12), Visit 6 (week 24) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Clinical worsening defined as a decrease of 6MWT distance of more than 20% from baseline due to CTEPH, decrease of NYHA functional class, hospitalization with the requirement for additional PH specific treatment and/or death due to worsening CTEPH 2. Change in 6 MWT after 12 weeks 3. Change in maximal Borg score, heart rate and oxygen saturation during 6MWT 4. Change in WHO functional class 5. Change in MINNESOTA QOL instrument Exploratory: 1. Change in pro-BNP levels after 24 weeks 2. Change in hemodynamic parameters 3. Change in signs & symptoms;Timepoint(s) of evaluation of this end point: 1. troughout the trial 2. Baseline, Visit 4 (12 weeks), Visit 6 (24 weeks) 3. Baseline, Visit 4 (12 weeks), Visit 6 (24 weeks) 4. Baseline, Visit 4 (12 weeks), Visit 6 (24 weeks) 5. Baseline, Visit 4 (12 weeks), Visit 6 (24 weeks) Exploratory: 1. Baseline, Visit 6 (24 weeks) 2. Baseline, Visit 6 (24 weeks) 3. Baseline, Visit 4 (12 weeks), Visit 6 (24 weeks) | — |
Countries
Austria, Czech Republic, Germany, Poland, Slovakia
Outcome results
None listed