Evaluation of the effect of ambrisentan on digital microvascular flow in patients with systemic sclerosis using laser Doppler perfusion imaging: a 12-week randomized double-blind placebo controlled trial

Abstract

Introduction: In patients with systemic sclerosis (SSc), digital ischemia results from an occlusive microvasculopathy that may not respond adequately to conventional vasodilators. Endothelin receptor antagonists can potentially modify the fibroproliferative vascular remodeling in SSc, and hence their use may be justified in the management of digital ischemia. The objective of this clinical trial was to evaluate the effect of ambrisentan, a selective endothelin type A receptor antagonist, on microvascular blood flow in patients with limited systemic sclerosis (SSc) using laser Doppler perfusion imaging (LDPI).

Methods: In this randomized, double-blind, placebo controlled study we enrolled 20 patients with limited SSc. Fifteen patients received ambrisentan 5 mg daily for one month and then 10 mg daily for two months, and five received a placebo. There were three visits: weeks 0 (baseline), one and 12. Three patient-oriented questionnaires were completed at each visit: Scleroderma-Health Assessment Questionnaire (S-HAQ), Raynaud Condition Score (RCS), and Pain-Visual Analog Scale (P-VAS). At each visit, LDPI was used to obtain three blood flow readings involving regions of interest in second to fifth fingers of the non-dominant hand at room temperature (25°C) and after cooling (10°C) for two minutes.

Results: There were 16 females (80%); mean age was 50 years. None of the differences in blood flow (as measured by LDPI) were significant both at baseline and after cooling. However, patients in the ambrisentan group showed significant improvement in the patient-oriented outcomes: RCS (P=0.001) and S-HAQ score (P=0.005).

Conclusions: This pilot study did not show evidence of significant increase in digital blood flow over time; however, there was an improvement in RCS and S-HAQ score. We conclude that continuous use of ambrisentan for three months does not seem to significantly improve digital blood flow in SSc patients.

Trial registration: Clinicaltrials.gov NCT01072669. Registered 19 February 2010.

Figures

Figure 1

Trial profile.

Figure 2

Boxplots showing perfusion measures at normal temperature and during cold challenge, S-HAQ scores, RCS and P-VAS scores. (A) Boxplots showing perfusion measures at baseline, week 1 and week 12 at normal temperature. Black boxes represent ambrisentan and gray boxes represent placebo. The bottom and top of the boxes represent the 25th and 75th percentiles, respectively; the band within the box is the median, and the ends of the whiskers are the minimum and maximum of all the data in that group; the square within the box is the mean. The dots on the left of each boxplot represent perfusion measures from individual subjects. (B) Boxplots showing perfusion measures at baseline, week 1 and week 12 during cold challenge. (C) Boxplots showing S-HAQ scores at baseline, week 1 and week 12. (D) Boxplots showing RCS at baseline, week 1 and week 12. (E) Boxplots showing P-VAS scores at baseline, week 1 and week 12. P-VAS, Pain-Visual Analog Score; RCS, Raynaud Condition Scale; s-HAQ, Scloderma-Health Assessment Questionnaire.