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 SSc with digital…
ID
Source
Brief title
Condition
- Autoimmune disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Mean of right and left carotid-femoral arterial (i.e. aortic) Pulse Wave
Velocity (cfPWV)
Secondary outcome
* Right and left carotid-brachial and carotid-radial arterial PWV (cbPWV and
crPWV)
* Local PWV of the right and left radial (rPWV), brachial (bPWV), femoral
(fPWV), and common carotid artery (cPWV)
* Mean intima media thickness (IMT) of right and left radial, brachial,
femoral, and common carotid artery
* Nail-fold Capillary Microscopy and derived indices: Microangiopathy Evolution
Score (MES), Capillaroscopic Skin Ulcer Risk Index (CSURI) and Prognostic Index
for Digital Laesions (PILD)
* Blood flow in the hands, and in different regions of the hands (region of
interest (ROI) 1, ROI 2 and ROI 3), as measured by Laser Doppler Perfusion
Imaging (LDPI) at standardised ambient hand temperature.
* Skin Autofluorescence
* Mean number of new DUs per and time to healing of the cardinal ulcer
* Urine albumin/creatinine ratio (ACR)
* Plasma NT-proBNP and uric acid
* Serum levels of matrix metalloproteinases (MMP 3 and MMP 9), and tissue
inhibitors of metalloproteinases (TIMP)
* Systolic, diastolic, and mean arterial blood pressure of the brachial artery
* Modified Rodnan Skin Score (mRSS)
* Scleroderma Health Assessment Questionnaire (SHAQ), EuroQol EQ-5D, and SF-36
Background summary
Digital ischemia is a major problem in patients with Raynaud*s phenomenon (RP),
especially in those with underlying connective tissue diseases (CTD) 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. Based on published research it is hypothesized that the
drug bosentan may improve vascular stiffness via different routes and thus to
reduce the number and severity of digital ulcers.
Study objective
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 SSc with
digital ulcers (DU) compared to a healthy controle group.
Study design
Randomized, prospective, 3-arm parallel group, open-label, (bosentan vs. usual
care only vs. no care), blinded endpoint (PROBE), intervention trial in 40
patients, and 20 healthy controls.
Intervention
Group 1: Usual care AND bosentan 62.5 mg twice daily, titrated to 125 mg twice
daily after one month if tolerated (n=20)
Group 2: Usual care only (n=20)
Group 3: healthy controls, no care (n=20)
Study burden and risks
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 the start in 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 3x 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.
Hanzeplein 1
Groningen 9713GZ
NL
Hanzeplein 1
Groningen 9713GZ
NL
Listed location countries
Age
Inclusion criteria
SSc patients
* 18 years or older
* Systemic sclerosis based on the 2013 ACR/EULAR criteria
* Raynaud*s phenomenon (RP)
* A history of digital ulcer disease
* Assessable Pulse Wave Velocity (PWV) measurement at baseline
* Written informed consent;Healthy controls:
* 18 years or older
* Written informed consent
Exclusion criteria
SSc patients:
* Hypersensitivity to the active substance or to any of the excipients
* Moderate to severe hepatic impairment, i.e., Child-Pugh class B or C
* Baseline values of liver aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT), 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 for example diabetes, dyslipidemia, systemic hypertension, coagulopathy;Healthy controls:
* Comorbidities
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-002796-28-NL |
| CCMO | NL49919.042.14 |