Bosentan in Systemic Sclerosis

Systemic Sclerosis Clinical Trial

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Official title:

Effects of Bosentan in a Homogenous Population of Systemic Sclerosis Subjects With a Predefined Restriction of Blood Flow in the Hands

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01395732
• Other study ID #: AC-052-427
• Status: Completed
• Phase: Phase 4
• First received: July 6, 2011
• Last updated: January 6, 2014
• Start date: March 2011
• Est. completion date: December 2012

Study information

• Verified date: January 2014
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Independent Ethics Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Digital Ulcers
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

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

Locations

Country	Name	City	State
Netherlands	VUmc	Amsterdam
Netherlands	UMC Groningen	Groningen
Netherlands	MCL	Leeuwarden
Netherlands	LUMC	Leiden
Netherlands	MUMC	Maastricht
Netherlands	UMC St Radboud	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Maasstad Ziekenhuis	Rotterdam
Netherlands	Sint Franciscus Gasthuis	Rotterdam
Netherlands	Isala Klinieken	Zwolle

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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.	Baseline to 12 weeks of bosentan treatment	No