Efficacy and Tolerability of Subcutaneously Administered Treprostinil Sodium in Patients With Severe (Non-operable) Chronic Thromboembolic Pulmonary Hypertension (CTREPH) (CTREPH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01416636
Recruitment Status : Active, not recruiting
First Posted : August 15, 2011
Last Update Posted : October 4, 2017
Information provided by (Responsible Party):
SciPharm SàRL

Brief Summary:
The primary purpose of this study it to determine the effect on 6 minute walking test (MWT) distance after 24 weeks treatment with subcutaneous (SC) Treprostinil Sodium in patients with Severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension.

Condition or disease Intervention/treatment Phase
Non-operable Chronic Thromboembolic Pulmonary Hypertension Drug: Treprostinil sodium Phase 3

Detailed Description:

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by non-resolving organized thromboembolic obstructing the pulmonary vascular bed (Lang, 1994). 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 (Klepetko, 2004)). 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) (McLaughlin, 2004), 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) (Kuhn, 2003), thrombosis and new major vessel thromboembolism.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double Blind Controlled Clinical Study to Investigate the Efficacy and Tolerability of Subcutaneous Treprostinil Sodium in Patients With Severe Non-operable Chronic Thromboembolic Pulmonary Hypertension (CTREPH)
Study Start Date : March 2009
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Arm Intervention/treatment
Experimental: Treprostinil sodium high dose Drug: Treprostinil sodium
Active Comparator: Treprostinil sodium low dose Drug: Treprostinil sodium

Primary Outcome Measures :
  1. To determine the effect of subcutaneous Treprostinil sodium on 6MWT distance after 24 weeks in patients with severe non-operable chronic thromboembolic pulmonary hypertension severe (inoperable) Chronic Thromboembolic Pulmonary Hypertension [ Time Frame: 24 weeks ]

Secondary Outcome Measures :
  1. To assess the time to clinical worsening [ Time Frame: 24 weeks ]
  2. To assess the effect on maximal Borg score, heart rate and oxygen saturation during 6MWT [ Time Frame: 24 weeks ]
  3. To assess the effect on WHO NYHA (World health organization- New York Heart Association) functional class [ Time Frame: 24 weeks ]
  4. To assess the effect on QOL (Quality of Life) by the MINNESOTA questionnaire [ Time Frame: 24 weeks ]
  5. To assess the effect on N-terminal pro-BNP levels [ Time Frame: 24 weeks ]
  6. To assess the effect on hemodynamic parameters (PVR, mPap, mRap (Mean right atrial pressure, CO (Cardiac Output), CI (Cardiac Index)) [ Time Frame: 24 weeks ]
  7. To assess the effect on signs & symptoms of the CTEPH [ Time Frame: 24 weeks ]
  8. To assess the treatment - emergent Adverse Events (AE's), Serious Adverse Events (SAE's) , AE's leading to discontinuation and relevant laboratory abnormalities [ Time Frame: 24 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
  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 PAPm of > 25 mmHg, and a PVR of > 300
    • 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/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 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


  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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01416636

Krankenhaus der Elisabethinen
Linz, Austria, 4020
Medical University of Vienna AKH - Division Cardiology
Vienna, Austria
II. interní klinika Všeobecná fakultní nemocnice
Prague, Czechia
Medical University Carl Gustav Carus Medizinische Klinik und Poliklinik I Medizinische Fakultät der Technischen Universität Dresden
Dresden, Germany
Department of Cardiac and Vascular Diseases Centre for Rare Cardiovascular Diseases John Paul II Hospital
Krakow, Poland, 31-202
NZOZ Europejskie Centrum Zdrowia Otwock
Otwock, Poland, 05-400
Sponsors and Collaborators
SciPharm SàRL
Principal Investigator: Irene Lang, MD Medical University Vienna

Responsible Party: SciPharm SàRL Identifier: NCT01416636     History of Changes
Other Study ID Numbers: 116-02
First Posted: August 15, 2011    Key Record Dates
Last Update Posted: October 4, 2017
Last Verified: October 2017

Additional relevant MeSH terms:
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Antihypertensive Agents