Treatment of Thromboangiitis Obliterans (Buerguer's Disease) With Bosentan

Treatment of Thromboangiitis Obliterans (Buerger's Disease) With Bosentan

This study assessed the effectiveness and safety of bosentan when administered to thromboangiitis obliterans (Buerger's disease)patients. A clinical pilot study was designed,included in which patients with ulcer and/or pain at rest were treated with bosentan p.o at a dose of 62,5 mg twice daily during the first month, which each thereafter uptitrated to 125 mg twice daily. Study endpoints were clinical improvement rate, major or minor amputation rate, hemodynamic changes, changes in endothelial function and angiographic changes.

12 patients were included were current smokers. With bosentan treatment, no new ischemic lesions were observed in all but one patient. Overall, clinical improvement was observed in 12 of the 13 extremities (92%). Only two of 13 extremities underwent amputation after bosentan treatment. As assessed by digital arteriography with subtraction or angio-magnetic resonance image an increase of distal flow was observed in 10 out of the 12 patients. All patients experienced a statistically significant improvement in their BAFMD values (means:1.8 at baseline;6.6 at the end of the treatment;12.7 three months after the end of the treatment;p<0.01). In conclusion: Bosentan treatment may result in an improvement of clinical, angiographic, hemodynamic and endothelial function outcome. Bosentan deserves further investigation in the management TAO patients.

Study Overview

• Status: Completed
• Conditions: Thromboangiitis Obliterans
• Intervention / Treatment: Drug: Bosentan

• Study Type: Observational
• Enrollment (Actual): 12

Contacts and Locations

Study Locations

• Spain
  • Getafe, Spain, 28901
    • Hospital Universitario de Getafe
  • Madrid
    • Getafe, Madrid, Spain, 28905
      • Hospital Universitario Getafe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients suffering from Buerger's disease

Description

Inclusion Criteria:

• Critical ischemia in any extremity, causing pain at rest or non-healing ischemic ulcers, present for at least four weeks with no evidence of improvement in response to conventional treatment.

Exclusion Criteria:

• Being candidates for surgical or endovascular revascularisation of the extremity studied.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bosentan	Drug: Bosentan; Bosentan therapy consisted of a month's treatment with 62.5 mg bid orally administered. Dose doubled to 125 mg bid after the first month. The full-dose regimen (125 mg/12h) was maintained for the following months or until total healing fo the ulcers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical improvement rate	Clinical improvement rate (absence of new throphic lesions, ulcer healing process, pain relief, complete absence of pain), major of minor amputation rate	4-6 months
Clinical improvement rate	Clinical improvement rate (abscence of new throphic lesions, ulcer healing process, pain relief, complete absence of pain), major of minor amputation rate	4-6 months
Clinical improvement rate	Clinical improvement rate (absence of new throphic lesions, ulcer healing process, pain relief, complete absense of pain), major of minor amputation rate	4-6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
haemodynamics, endothelial function and angiographic changes	Hemodynamic changes as measured by means of ABI, changes in endothelial funtion as measured by means of the brachial artery flow-mediated dilation test (BAFMD) and angiographic changes as measured by means of arteriography with digital substraction or an angio-magnetic resonance image (MRI).	4-6 months

Collaborators and Investigators

• Sponsor: Hospital Universitario Getafe
• Investigators: Principal Investigator: Joaquin De Haro, MD,PhD, Hospital Universitario de Getafe

Publications and helpful links

General Publications

• De Haro J, Bleda S, Acin F. An open-label study on long-term outcomes of bosentan for treating ulcers in thromboangiitis obliterans (Buerger's disease). Int J Cardiol. 2014 Dec 15;177(2):529-31. doi: 10.1016/j.ijcard.2014.08.107. Epub 2014 Aug 23. No abstract available.
• De Haro J, Acin F, Bleda S, Varela C, Esparza L. Treatment of thromboangiitis obliterans (Buerger's disease) with bosentan. BMC Cardiovasc Disord. 2012 Feb 14;12:5. doi: 10.1186/1471-2261-12-5.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): January 1, 2011
• Study Completion (Actual): January 1, 2011

Study Registration Dates

• First Submitted: October 5, 2011
• First Submitted That Met QC Criteria: October 5, 2011
• First Posted (Estimate): October 6, 2011

Study Record Updates

• Last Update Posted (Estimate): August 16, 2016
• Last Update Submitted That Met QC Criteria: August 15, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Bosentan; Buerguer disease
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Vasculitis; Thromboangiitis Obliterans; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Endothelin Receptor Antagonists; Bosentan
• Other Study ID Numbers: Buerger-Bosentan