The Clinical Efficacy And Subclinical Effects on Arterial STIFFNESS of Bosentan Therapy Added to Usual Care in Patients With Systemic Sclerosis With Digital Ulcers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave Velocity (cfPWV)
研究概览
简要总结
The aim of the study is to investigate whether bosentan added to usual care improves arterial stiffness after 3 months as measured as the pulse wave velocity (PWV) of the medium and large arteries corrected for blood pressure changes in patients with systemic sclerosis (SSc) with digital ulcers (DU). Patients will be randomized into a group with usual care and bosentan (n=10) or usual care only (n=10). PWV will be assessed at baseline, 3 months and 12 months.
详细描述
Rationale: Digital ischemia is a major problem in patients with Raynaud's phenomenon (RP), especially in those with underlying connective tissue diseases such as systemic sclerosis (SSc). SSc is hallmarked by microvascular disease which can be assessed by nailfold capillary microscopy (NCM) to identify specific capillary patterns. However, it appears that vascular damage is not restricted to the capillaries, but may also extend to more upstream hand and forearm arteries. This may not only be reflected by clinically relevant structural abnormalities such as obliteration, but also by decreases in arterial function. The best characterised in RP is the occurrence of vasospasms after cold exposure. However, evidence points out that major stiffening of the arteries also occurs, potentially exaggerating digital ischemia and other vascular complications in SSc.
Objective
To investigate whether bosentan added to usual care improves arterial stiffness after 3 months as measured as the pulse wave velocity of the medium and large arteries corrected for blood pressure changes in patients with systemic sclerosis with digital ulcers.
Intervention:
Group 1: Usual care AND bosentan 62.5 mg twice daily, titrated to 125 mg twice daily after one month if tolerated (n=10) Group 2: Usual care only (n=10)
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Bosentan is a registered product in the Netherlands. In this study, it will be used within its indication and not in combination with other products for which it has not been registered. Therefore no additional unknown uncertainties and increased overall risk are applicable for the investigational product. In the usual care group, treatment will not differ from clinical practice. To minimize the risk of patients not receiving the most appropriate treatment in the control group, regular visits and lab assessments are planned. Patients are allowed to start with bosentan in the usual care group if indicated by the treating physician. The study will consist of one screening and three study visits. During the latter, patients clinical signs and symptoms will be assessed, vascular lab will be performed, blood will be drawn, and subjects be asked to fill in questionnaire, all of which will have a duration of no more than 2 hours per visits. In total 3 times 24cc of blood will be collected, preferably in combination will routine lab assessments. These measures render the risks acceptable and the burden minimal for the subjects participating in the study.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18 years or older
- •Systemic sclerosis based on the 2013 American College of Rheumatology/European League Against Rheumatism criteria
- •Raynaud's phenomenon
- •A history of digital ulcer disease
- •Assessable Pulse Wave Velocity measurement at baseline
- •Written informed consent
排除标准
- •Hypersensitivity to the active substance or to any of the excipients
- •Systolic blood pressure lower than 85 mmHg
- •Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C
- •Baseline values of liver aminotransferases, i.e., aspartate aminotransferases and/or alanine aminotransferases, greater than 3 times the upper limit of normal
- •Concomitant use of cyclosporine A
- •Pregnancy
- •Women of child-bearing potential who are not using reliable methods of contraception
- •Significant peripheral vascular disease as the sole consequence of atherosclerotic disease due to conventional vascular risk factors and coagulopathy
研究组 & 干预措施
Usual care and bosentan
Usual care and also treatment with bosentan.
干预措施: bosentan (Drug)
结局指标
主要结局
Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave Velocity (cfPWV)
时间窗: 3 months
assessed with Sphygmocor
次要结局
- Capillaroscopic Skin Ulcer Risk Index (CSURI)(3 and 12 months)
- Number of new digital ulcers(3 and 12 months)
- Time to healing of digital ulcers(3 and 12 months)
- Right carotid-brachial arterial PWV (cbPWV)(3 and 12 months)
- Right carotid-radial arterial PWV (crPWV)(3 and 12 months)
- Microangiopathy Evolution Score (MES)(3 and 12 months)
- Prognostic Index for Digital Lesions (PILD)(3 and 12 months)
- Local PWV of the right radial artery (rPWV)(3 and 12 months)
- Local PWV of the left radial artery (rPWV)(3 and 12 months)
- Local PWV of the right brachial artery (bPWV)(3 and 12 months)
- Skin Autofluorescence(3 and 12 months)
- Serum levels of tissue inhibitors of metalloproteinases (TIMP)(3 and 12 months)
- Blood pressure of the brachial artery(3 and 12 months)
- Modified Rodnan Skin Score (mRSS)(3 and 12 months)
- Scleroderma Health Assessment Questionnaire (SHAQ)(3 and 12 months)
- Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave Velocity (cfPWV)(12 months)
- Local PWV of the left brachial artery (bPWV)(3 and 12 months)
- Mean widened capillaries of 8 fingers (dig 2-5)(3 and 12 months)
- Mean giant capillaries of 8 fingers (dig 2-5)(3 and 12 months)
- Left carotid-brachial arterial PWV (cbPWV)(3 and 12 months)
- Left carotid-radial arterial PWV (crPWV)(3 and 12 months)
- Mean loop width of 8 fingers (dig 2-5)(3 and 12 months)
- Blood flow in the hands in region of interest (ROI) 1: distal of the proximal interphalangeal (PIP) joint of the 3 middle fingers(3 and 12 months)
- Blood flow in the hands in ROI 2: distal of the metacarpal joints and proximal of the PIP joint(3 and 12 months)
- Urine albumin/creatinine ratio (ACR)(3 and 12 months)
- Serum levels of matrix metalloproteinases 9(3 and 12 months)
- Mean capillary density of 8 fingers (dig 2-5)(3 and 12 months)
- Blood flow in the hands in ROI 3: the hand proximal of the metacarpal joints(3 and 12 months)
- Serum levels of matrix metalloproteinase 3(3 and 12 months)
- Short Form (36)(3 and 12 months)
- Plasma N-terminal of the prohormone brain natriuretic peptide (NT-proBNP)(3 and 12 months)
研究者
dr. DJ Mulder
dr. Douwe J. Mulder
University Medical Center Groningen