Treatment With Endothelin Antagonist to Tcpc Patients; a Multicenter, Randomized, Prospective Study Measuring Maximal O2 Uptake in Ergometer Bicycle Test
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 4
- 主要终点
- Change from baseline in VO2max at 14 weeks
研究概览
简要总结
The purpose of this study is to determine whether Bosentan is an effective and safe treatment to adolescent and adult (15 years and older) patients, born with one ventricle of the heart instead of two (single ventricle physiology) and who have undergone TCPC as a palliative surgical treatment. The aim of the TCPC operation is to use the one functioning ventricle to pump the blood flow to the body, while the blood to the lungs is received directly from the caval veins, and is thus a passive flow, without the aid of a ventricle to actively pump the blood through the pulmonary circulation. The resistance in the pulmonary circulation is therefore critical to these patients. These patients have markedly lower work capacity in bicycle test than the general public. Furthermore they have a high risk of developing complications e.g. loss of protein from the intestines.
Bosentan is a medication that lowers the resistance in the pulmonary circulation. It is routinely used for patients with pulmonary hypertension. Some studies have shown that drugs that lower the pulmonary resistance can increase exercise capacity significantly in patients with single ventricle physiology.
In this study 80 patients will receive either placebo or Bosentan for 14 weeks. Before and after the treatment, bicycle test along with blood samples, stool samples and quality of life interviews will be performed. Every four weeks during the study blood samples, physical exam and interviews will be performed to ensure the safety of the treatment.
The investigators expect to find a significant increase in work capacity after 14 weeks in the treatment group compared with the placebo group.
Moreover the investigators hope to find a decrease in intestinal protein loss and an improved quality of life.
详细描述
In the statistical analysis the investigators wish to analyse interactions between the primary endpoint and predefined subgroups in order to distinguish responders from non-responders to the treatment. The predefined subgroups are:
NT-proBNP > 100 (yes/no) Ventricular anatomy (RV/LV) CT-proEndothelin-1. In the latter, the investigators do not wish to predefine a specific value, due to limited experience with this analysis. We wish to use the data from the study to find a cut-off value, that is able to predict positive response to treatment.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •TCPC operated
- •Age > 15 years old
- •Clinical stability > 3 months, evaluated by investigator from clinical record
- •For women: Negative s-hCG and use of contraception
排除标准
- •Severe heart failure (NYHA-class IV)
- •Oxygen saturation < 85 % at rest
- •Pre-existing liver condition (transaminases 2x > reference)
- •Renal failure (creatinin > 150 mmol/l)
- •Obstruction of TCPC circulation
- •History of work induced severe arrhythmia
- •Systolic blood pressure below 80% of reference (BT < 88 mmHg)
- •Use of any of following drugs: Fluconazol, Ketoconazole, CiclosporinA, Lopinavir, Ritonavir, Rifampicin, Carbamazepin and Phenytoin
- •Significant extra-cardiac condition e.g. neurological impairment
研究组 & 干预措施
Bosentan
干预措施: Bosentan (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in VO2max at 14 weeks
时间窗: Baseline and 14 weeks
Maximal O2 uptake in ml/min/kg in ergometer bicycle test
次要结局
- Change from baseline in blood samples at 14 weeks(Baseline and 14 weeks)
- Change from baseline in SF36 questionnaire score at 14 weeks(Baseline and 14 weeks)
- Change from baseline in feces alfa 1 antitrypsin at 14 weeks(Baseline and 14 weeks)
- Number of participants with adverse events(2, 6, 10 and 14 weeks after start of treatment)
- Change from baseline in vital signs(Baseline, 2, 6, 10 and 14 weeks)
- Change from baseline in control blood samples(Baseline, 2, 6, 10 and 14 weeks)
- Change from baseline in cardiac output/pulmonary blood flow(Baseline and 14 weeks)
研究者
Anders Hebert
M.D.
Rigshospitalet, Denmark