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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 105
- 试验地点
- 6
- 主要终点
- Change in 6-minute Walk Test Distance After 24 Weeks
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Treprostinil sodium low dose - Arm I
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.
干预措施: Treprostinil sodium (Drug)
Treprostinil sodium high dose - Arm II
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.
干预措施: Treprostinil sodium (Drug)
结局指标
主要结局
Change in 6-minute Walk Test Distance After 24 Weeks
时间窗: 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.
次要结局
- Number of Participants With Clinical Worsening(12 weeks and 24 weeks)
- Effect on Maximal Borg Score During 6-minutes Walk Test(Baseline and 24 weeks)
- Change in WHO/NYHA (World Health Organization - New York Heart Association) Functional Class(Baseline and 24 weeks)
- Effect on N-terminal Pro-BNP Levels(Baseline and 24 weeks)
- Effect on Quality of Life by the MINNESOTA Questionnaire(Baseline and 24 weeks)
- Effect on Hemodynamic Parameter (PVR - Pulmonary Vascular Resistance)(Baseline and 24 weeks)
- Effect on Hemodynamic Parameter (CI - Cardiac Index)(Baseline and 24 weeks)
- Effect on Hemodynamic Parameter (mPAP - Mean Pulmonary Arterial Pressure)(Baseline and 24 weeks)
- Effect on Hemodynamic Parameter (CO - Cardiac Output)(Baseline and 24 weeks)
- Effect on Hemodynamic Parameter (mRap - Mean Right Atrial Pressure)(Baseline and 24 weeks)
- Effect on Signs & Symptoms of the CTEPH(Baseline and 24 weeks)