The primary objectives are:- To demonstrate the relationship of blood flow in the hands and the extent of digital ulcera in patients with systemic scleroderma;- Evaluate the effect of bosentan on the blood flow in the hands from baseline to 12 weeks…
ID
Source
Brief title
Condition
- Connective tissue disorders (excl congenital)
- Skin vascular abnormalities
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- Relationship between blood flow in the hands, as measured by laser Doppler
imaging, and extent of digital ulcera assessed by the mean blood flow
restriction in four distinct groups of patients: patients without current
digital ulcera (pitting scars allowed), patients with new digital ulcera (less
than 3 months old), patients with persistent digital ulcera (more than 3 months
old) and patients with significant tip-necrosis;
- Change in blood flow in the hands after 12 weeks of bosentan treatment
compared to the blood flow at 0 weeks, as measured by laser Doppler imaging.
Secondary outcome
- Change in blood flow in different regions of the hands after 4 and 12 weeks
of bosentan treatment compared to the blood flow after 0 weeks, as measured by
laser Doppler imaging;
- Change in modified Rodnan Skin Score (mRSS) from 0 weeks to 12 weeks, 26
weeks and 52 weeks of bosentan treatment;
- Change in selected components of the Scleroderma Health Assessment
Questionnaire from 0 weeks to 12 weeks, 26 weeks and 52 weeks of bosentan
treatment;
- Changes in EQ 5D from 0 weeks to 12 weeks, 26 weeks and 52 weeks of bosentan
treatment;
- Total number of new DU and pitting scars developed from 0 weeks to 12 weeks,
26 weeks and 52 weeks of bosentan treatment.
Background summary
The effect of bosentan on digital ulcers (DU) was studied in two randomized
placebo-controlled trials (RAPIDS-1 and RAPIDS-2). A limitation of these
studies was the heterogeneous study population. More importantly, there were no
endpoints that assessed changes in vasculopathy and / or perfusion. Laser
Doppler imaging has been shown to effectively demonstrate blood flow
restrictions in the hands of patients with Systemic Scleroderma (SSc) (Rosato
et al, 2010).
This study has been set up to demonstrate the relation between the blood flow
in the hands and the extent of the digital ulcera in patients with systemic
scleroderma.
In addition, the impact of bosentan on the blood flow in the hands, in a
defined cohort of systemic scleroderma patients with a history of digital
ulcera within the past 2 years and a clinically relevant reduction of blood
flow in the hands, will be assessed.
Study objective
The primary objectives are:
- To demonstrate the relationship of blood flow in the hands and the extent of
digital ulcera in patients with systemic scleroderma;
- Evaluate the effect of bosentan on the blood flow in the hands from baseline
to 12 weeks, measured by laser Doppler imaging, in systemic scleroderma
patients with a history of digital ulcera in the past 2 years and a clinically
relevant reduction of blood flow at baseline.
The secondary objectives are:
- To evaluate the effect of bosentan on the blood flow in different regions of
the hands from 0 weeks to 4 weeks and 12 weeks;
- To evaluate the effect of bosentan on the hand function, pain perception and
quality of life from 0 weeks to 12 weeks, 26 weeks and 52 weeks;
- To evaluate the effect of bosentan on the modified Rodnan Skin Score from 0
weeks to 12 weeks, 26 weeks and 52 weeks;
- To evaluate the effect of bosentan on the development of new digital ulcera
and pitting scars from 0 weeks to 12 weeks, 26 weeks and 52 weeks.
Study design
Open label, non comparative study.
Intervention
Patients that will be included in the study will start bosentan treatment as
described in the summary of product characteristics. After 12 weeks of
treatment the investigator/treating physician decides, together with the
patient, if the bosentan treatment will be continued (for as long as needed).
Study burden and risks
The patients will visit the hospital 5 times (after 0, 4, 12, 26 and 52 weeks)
as a result of participating in this study. During visit 1, 2 and 3 the blood
flow in the hands will be measured by laser Doppler imaging. During visit 1, 3,
4 and 5 the patient will be asked to complete 2 questionnaires (selected
components of the SHAQ and the EQ 5D) and the investigator completes 1
questionnaire (modified Rodnan Skin Score).
Next to the known risks of treatment with bosentan there are no significant
risks to participation in this study and the burden is minimal, compared to the
advantage the patient might experience from treatment with bosentan.
Beneluxlaan 2b
3446 GR Woerden
NL
Beneluxlaan 2b
3446 GR Woerden
NL
Listed location countries
Age
Inclusion criteria
1. Male and female subjects > 18 years diagnosed with systemic sclerosis;
2. Reduction of blood flow measured by laser Doppler imaging, of at least 50%, distally to the proximal interphalangeal joint, compared to historical healthy controls;
3. Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception;
4. A history of 1 or more DUs within 2 years prior to inclusion;
5. No use of bosentan in the past;
6. Subjects willing and able to sign informed consent.
Exclusion criteria
1. Parenteral Prostanoid treatment for DU < 3 months ago;
2. Chronic treatment with PDE-5 inhibitor or ERA;
3. History of bosentan use;
4. Irreversible significant limitation of the hand function, e.g. amputation of more than one finger;
5. Other types of system- or connective tissue diseases;
6. Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy;
7. Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months;
8. Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN);
9. Moderate to severe liver function disorder;
10. Pregnancy or breastfeeding;
11. Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors;
12. Hypersensitivity for bosentan or one of its components;
13. Subjects not able to follow the protocol.
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 | EUCTR2010-023908-27-NL |
| CCMO | NL34698.091.10 |