Bosentan in Systemic Sclerosis (HOME)
Primary Purpose
Systemic Sclerosis, Digital Ulcers
Status
Completed
Phase
Phase 4
Locations
Netherlands
Study Type
Interventional
Intervention
Bosentan
Sponsored by
About this trial
This is an interventional treatment trial for Systemic Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Male and female subjects > 18 years diagnosed with SSc;
- Reduction of blood flow measured by laser Doppler imaging, of at least 50%, distally to the proximal interphalangeal joint, compared to the healthy volunteers;
- Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception;
- A history of 1 or more DUs within 2 years prior to inclusion;
- No use of bosentan in the past;
- Subjects willing and able to sign informed consent.
Exclusion Criteria:
- Parenteral prostanoid treatment for DU < 3 months ago;
- Chronic treatment with PDE-5 inhibitor or ERA;
- History of bosentan use
- Irreversible significant limitation of the hand function, e.g. amputation of more than one finger;
- Other types of system- or connective tissue diseases;
- Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy;
- Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months;
- Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN);
- Moderate to severe liver function disorder;
- Pregnancy or breastfeeding;
- Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors;
- Hypersensitivity for bosentan or one of its components;
- Subjects not able to follow the protocol.
Sites / Locations
- VUmc
- UMC Groningen
- MCL
- LUMC
- MUMC
- UMC St Radboud
- Erasmus MC
- Sint Franciscus Gasthuis
- Maasstad Ziekenhuis
- Isala Klinieken
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
Mean blood flow restriction in patients
Relationship between blood flow in the hands, as measured by laser Doppler imaging, and extent of Digital Ulcer disease assessed by the mean blood flow restriction in four distinct groups of patients: patients without current Digital Ulcers (pitting scars allowed), patients with new Digital Ulcers (< 3 months), patients with persistent Digital Ulcers (> 3 months) and patients with significant tip-necrosis.
Secondary Outcome Measures
Change in blood flow in the hands
Change in blood flow in the hands after 12 weeks of bosentan treatment compared to the baseline, as measured by laser Doppler imaging.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01395732
Brief Title
Bosentan in Systemic Sclerosis
Acronym
HOME
Official Title
Effects of Bosentan in a Homogenous Population of Systemic Sclerosis Subjects With a Predefined Restriction of Blood Flow in the Hands
Study Type
Interventional
2. Study Status
Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Actelion
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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 Sclerosis (SSc). The relation between blood flow restriction in the hands measured by laser Doppler imaging and the extent of DU disease has not been studied. The current study will attempt to demonstrate this relation. In addition, the impact of bosentan on the blood flow in the hands, in a defined cohort of SSc-DU patients with a history of DU within the past 2 years and a clinically relevant reduction of blood flow in the hands, will be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Systemic Sclerosis, Digital Ulcers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Bosentan
Intervention Description
2 tablets of 62.5 mg a day from baseline to week 4, then 2 tablets of 125 mg per day to week 12.
Primary Outcome Measure Information:
Title
Mean blood flow restriction in patients
Description
Relationship between blood flow in the hands, as measured by laser Doppler imaging, and extent of Digital Ulcer disease assessed by the mean blood flow restriction in four distinct groups of patients: patients without current Digital Ulcers (pitting scars allowed), patients with new Digital Ulcers (< 3 months), patients with persistent Digital Ulcers (> 3 months) and patients with significant tip-necrosis.
Time Frame
Baseline to 12 weeks
Secondary Outcome Measure Information:
Title
Change in blood flow in the hands
Description
Change in blood flow in the hands after 12 weeks of bosentan treatment compared to the baseline, as measured by laser Doppler imaging.
Time Frame
Baseline to 12 weeks of bosentan treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male and female subjects > 18 years diagnosed with SSc;
Reduction of blood flow measured by laser Doppler imaging, of at least 50%, distally to the proximal interphalangeal joint, compared to the healthy volunteers;
Women of childbearing potential must have a negative pregnancy test and use a reliable form of contraception;
A history of 1 or more DUs within 2 years prior to inclusion;
No use of bosentan in the past;
Subjects willing and able to sign informed consent.
Exclusion Criteria:
Parenteral prostanoid treatment for DU < 3 months ago;
Chronic treatment with PDE-5 inhibitor or ERA;
History of bosentan use
Irreversible significant limitation of the hand function, e.g. amputation of more than one finger;
Other types of system- or connective tissue diseases;
Significant peripheral (macro-) vascular disease due to e.g. diabetes, hyperlipidemia, uncontrolled systemic hypertension, coagulopathy;
Any serious medical co morbidity (eg, active malignancy) such that the subjects life expectancy is < 12 months;
Known AST and/or ALT elevations higher than 3 times Upper Limit Normal (ULN);
Moderate to severe liver function disorder;
Pregnancy or breastfeeding;
Treatment with Glibenclamide, Fluconazole, Cyclosporin A, Tacrolimus or other calcineurin inhibitors;
Hypersensitivity for bosentan or one of its components;
Subjects not able to follow the protocol.
Facility Information:
Facility Name
VUmc
City
Amsterdam
ZIP/Postal Code
10811HV
Country
Netherlands
Facility Name
UMC Groningen
City
Groningen
ZIP/Postal Code
9700RB
Country
Netherlands
Facility Name
MCL
City
Leeuwarden
ZIP/Postal Code
8934AD
Country
Netherlands
Facility Name
LUMC
City
Leiden
ZIP/Postal Code
2333ZA
Country
Netherlands
Facility Name
MUMC
City
Maastricht
ZIP/Postal Code
6229HX
Country
Netherlands
Facility Name
UMC St Radboud
City
Nijmegen
ZIP/Postal Code
6525GA
Country
Netherlands
Facility Name
Erasmus MC
City
Rotterdam
ZIP/Postal Code
3015CE
Country
Netherlands
Facility Name
Sint Franciscus Gasthuis
City
Rotterdam
ZIP/Postal Code
3045PM
Country
Netherlands
Facility Name
Maasstad Ziekenhuis
City
Rotterdam
ZIP/Postal Code
3078HT
Country
Netherlands
Facility Name
Isala Klinieken
City
Zwolle
ZIP/Postal Code
8011JW
Country
Netherlands
12. IPD Sharing Statement
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Bosentan in Systemic Sclerosis
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