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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by SciPharm SàRL
Sponsor:
Information provided by (Responsible Party):
SciPharm SàRL
ClinicalTrials.gov Identifier:
NCT01416636
First received: August 12, 2011
Last updated: January 20, 2014
Last verified: August 2013
  Purpose

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 Intervention Phase
Non-operable Chronic Thromboembolic Pulmonary Hypertension
Drug: Treprostinil sodium
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by SciPharm SàRL:

Primary Outcome Measures:
  • 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:
  • To assess the time to clinical worsening [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • To assess the effect on maximal Borg score, heart rate and oxygen saturation during 6MWT
  • To assess the effect on WHO NYHA (World health organization- New York Heart Association) functional class [ Time Frame: 24 weeks ]
  • To assess the effect on QOL (Quality of Life) by the MINNESOTA questionnaire
  • To assess the effect on N-terminal pro-BNP levels [ Time Frame: 24 weeks ]
  • To assess the effect on hemodynamic parameters (PVR, mPap, mRap (Mean right atrial pressure, SVR (Systemic Vascular Resistance), CO (Cardiac Output), CI (Cardiac Index)) [ Time Frame: 24 weeks ]
  • To assess the effect on signs & symptoms of the CTEPH [ Time Frame: 24 weeks ]
  • 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 ] [ Designated as safety issue: Yes ]

Study Start Date: March 2009
Estimated Study Completion Date: December 2014
Arms Assigned Interventions
Experimental: Treprostinil sodium high dose Drug: Treprostinil sodium
Active Comparator: Treprostinil sodium low dose Drug: Treprostinil sodium

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
    • 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 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 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01416636

Contacts
Contact: Bianca Tan, MSc 00436649639319 b.tan@scipharm.eu

Locations
Austria
Krankenhaus der Elisabethinen Recruiting
Linz, Austria, 4020
Medical University of Vienna AKH - Division Cardiology Recruiting
Vienna, Austria
Czech Republic
II. interní klinika Všeobecná fakultní nemocnice Recruiting
Prague, Czech Republic
Germany
Medical University Carl Gustav Carus Medizinische Klinik und Poliklinik I Medizinische Fakultät der Technischen Universität Dresden Terminated
Dresden, Germany
Poland
Department of Cardiac and Vascular Diseases Centre for Rare Cardiovascular Diseases John Paul II Hospital Recruiting
Krakow, Poland, 31-202
NZOZ Europejskie Centrum Zdrowia Otwock Active, not recruiting
Otwock, Poland, 05-400
Sponsors and Collaborators
SciPharm SàRL
Investigators
Principal Investigator: Irene Lang, MD Medical University Vienna
  More Information

No publications provided

Responsible Party: SciPharm SàRL
ClinicalTrials.gov Identifier: NCT01416636     History of Changes
Other Study ID Numbers: 116-02
Study First Received: August 12, 2011
Last Updated: January 20, 2014
Health Authority: Austria: Federal Ministry for Health and Women

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Treprostinil
Antihypertensive Agents
Cardiovascular Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014