Bosentan in Systemic Sclerosis

NCT01395732 | Completed Phase 4

• 1 other identifier: AC-052-427
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Systemic Sclerosis; Digital Ulcers

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline to 12 weeks

Secondary Outcomes (1)

• Change in blood flow in the hands

  Baseline to 12 weeks of bosentan treatment

Study Arms (1)

1

EXPERIMENTAL

Drug: Bosentan

Interventions

Bosentan DRUG

2 tablets of 62.5 mg a day from baseline to week 4, then 2 tablets of 125 mg per day to week 12.

1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• No use of bosentan in the past;
• Subjects willing and able to sign informed consent.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

MeSH Terms

Conditions

Scleroderma, Systemic; digital ulcers

Interventions

Bosentan

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2011
• First Posted: July 18, 2011
• Study Start: March 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 3, 2025

Record last verified: 2025-01