Early Venous Reflux Ablation (EVRA) Ulcer Trial: Baseline Characteristics and Event Rates

Abstract

The timing of offering superficial venous intervention to patients in terms of leg ulcer healing is controversial. Standard care in the United Kingdom derived from the 2007 Effect of Surgery and Compression on Healing and Recurrence (ESCHAR) trial involves compression bandaging to heal the ulcer followed by surgery to treat the underlying reflux to reduce the recurrence risk. The American Venous Forum has made the Grade 2, Level C recommendation in favor of early intervention in active ulceration based on the results of some cohort studies despite the randomized controlled trial evidence that there is no benefit. A trial has been designed to clarify this issue. This is a multicenter, prospective, randomized controlled trial funded by the National Institute for Health Research Health Technology Assessment Programme (project No. 11/129/197). The sample size of 450 patients was based on the primary outcome of time to ulcer healing. According to previous published literature, the 24-week healing rate in patients randomized to compression alone was approximately 60%. To calculate a sample size for this study, we estimated a benefit associated with early treatment of around 15%. Incorporating dropouts, 208 subjects per group are required (254 events in total) to identify a difference of 60% vs 75% in 24-week healing rates with 90% power. Patients are randomized to either early endovenous treatment of superficial venous reflux in addition to standard care or standard care alone. All patients are seen in an outpatient clinic at 6 weeks and examined clinically (with a duplex ultrasound scan taken in the early group), in addition to monthly telephone follow-ups to document resource use for the health economic analysis and to monitor patient safety. Weekly ulcer healing verification visits are performed on notification of healing. Quality of life is measured at baseline, 6 weeks, 6 months, and 12 months. The trial closed to recruitment on September 30, 2016. There were 5866 patients (51% men, 49% women; mean age, 72 years) who were screened, with 450 patients randomized (8% inclusion rate; 56% men, 44%women; mean age, 68 years); 27% of patients screened were ineligible with respect to ulcer duration and 6% declined to take part. The median baseline ulcer duration was 3.1 months, and the median size was 3.0 cm2 (interquartile range, 1.5-6.8) with a venous incompetence pattern of 56% great saphenous vein incompetence alone, 13% small saphenous vein incompetence alone, and 25% both great saphenous vein and small saphenous vein incompetence combined; 27% had evidence of deep venous incompetence. In the early arm, the interventional treatment strategy employed was 53% by foam alone, 26% with endothermal ablation alone, and 20% by a combination of therapies. To date, a total of 356 (81%) ulcers have healed within 12 months. This study will be the first large randomized multicenter trial to report on the clinical outcomes, quality of life, and cost-effectiveness of treating patients with venous ulcers by early superficial venous intervention.