HOME: Bosentan in Systemic Sclerosis

Sponsor

Actelion (Industry)

Overall Status

Completed

CT.gov ID

NCT01395732

Collaborator

(none)

Enrollment

Locations

Arm

21.1

Duration (Months)

1.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Systemic Sclerosis Digital Ulcers	Drug: Bosentan	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2011

Actual Primary Completion Date :

Nov 1, 2012

Actual Study Completion Date :

Dec 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	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.

Arm

Intervention/Treatment

Experimental: 1

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.

Outcome Measures

Primary Outcome Measures

Mean blood flow restriction in patients [Baseline to 12 weeks]
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 [Baseline to 12 weeks of bosentan treatment]
Change in blood flow in the hands after 12 weeks of bosentan treatment compared to the baseline, as measured by laser Doppler imaging.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	VUmc	Amsterdam	Netherlands	10811HV
2	UMC Groningen	Groningen	Netherlands	9700RB
3	MCL	Leeuwarden	Netherlands	8934AD
4	LUMC	Leiden	Netherlands	2333ZA
5	MUMC	Maastricht	Netherlands	6229HX
6	UMC St Radboud	Nijmegen	Netherlands	6525GA
7	Erasmus MC	Rotterdam	Netherlands	3015CE
8	Sint Franciscus Gasthuis	Rotterdam	Netherlands	3045PM
9	Maasstad Ziekenhuis	Rotterdam	Netherlands	3078HT
10	Isala Klinieken	Zwolle	Netherlands	8011JW

Sponsors and Collaborators

Actelion

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Actelion

ClinicalTrials.gov Identifier:

NCT01395732

Other Study ID Numbers:

AC-052-427

First Posted:

Jul 18, 2011

Last Update Posted:

Jan 7, 2014

Last Verified:

Jan 1, 2014

Additional relevant MeSH terms:

Scleroderma, Systemic

Scleroderma, Diffuse

Sclerosis

Bosentan

Study Results

No Results Posted as of Jan 7, 2014