Efficacy and Tolerability of Subcutaneously Administered Treprostinil Sodium in Patients With Severe (Non-operable) Chronic Thromboembolic Pulmonary Hypertension (CTREPH)
Condition: Non-operable Chronic Thromboembolic Pulmonary Hypertension
MeSH terms: Hypertension, Pulmonary; Hypertension
Intervention: Treprostinil sodium
Intervention MeSH terms: Treprostinil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 105.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

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.
    

Eligibility 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