Efficacy and Tolerability of Subcutaneously Administered Treprostinil Sodium in Patients With Severe (Non-operable) Chronic Thromboembolic Pulmonary Hypertension (CTREPH)
- Conditions
- Non-operable Chronic Thromboembolic Pulmonary Hypertension
- Interventions
- Registration Number
- NCT01416636
- Lead Sponsor
- SciPharm SàRL
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 105
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treprostinil sodium low dose - Arm I Treprostinil sodium Arm I (low dose): Subject was treated with a low dose of Treprostinil sodium. Dose was escalated to an approximate target dose of 3 ng/kg/min after the first 12 weeks and was kept stable for another 12 weeks. Due to the predefined infusion rate setting schedule an interim dose of up to 6 ng/kg/min could be reached for few days at the end of the phases 1,2 and 3. This depended on the patient's exact weight and is caused by the limited infusion rate setting possibility of the infusion pump. Treprostinil sodium high dose - Arm II Treprostinil sodium Subject was treated with a low dose of Treprostinil sodium. Dose was escalated to an approximate target dose of 3 ng/kg/min after the first 12 weeks and kept stable for another 12 weeks. Due to the predefined infusion rate setting schedule an interim dose of up to 6 ng/kg/min could be reached for few days at the end of the phases 1,2 and 3. This depended on the patient's exact weight and is caused by the limited infusion rate setting possibility of the infusion pump.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 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 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 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 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.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.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 (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 (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
Trial Locations
- Locations (6)
Krankenhaus der Elisabethinen
🇦🇹Linz, Austria
II. interní klinika Všeobecná fakultní nemocnice
🇨🇿Prague, Czechia
NZOZ Europejskie Centrum Zdrowia Otwock
🇵🇱Otwock, Poland
Medical University Carl Gustav Carus Medizinische Klinik und Poliklinik I Medizinische Fakultät der Technischen Universität Dresden
🇩🇪Dresden, Germany
Medical University of Vienna AKH - Division Cardiology
🇦🇹Vienna, Austria
Department of Cardiac and Vascular Diseases Centre for Rare Cardiovascular Diseases John Paul II Hospital
🇵🇱Krakow, Poland