EVRA Trial Shows Benefits of Early Endovenous Ablation in Venous Ulcer Healing

April 24, 2018—Investigators from the Early Venous Reflux Ablation (EVRA) trial presented and published findings indicating that early endovenous ablation of superficial venous reflux as an adjunct to compression therapy resulted in shorter time to ulcer healing versus compression therapy alone. Additionally, patients receiving early treatment had longer ulcer-free time during the year following randomization, and early intervention was also shown to be a cost-effective strategy. The data were presented at the Charing Cross International Symposium in London, England, and simultaneously published by Manjit S. Gohel, MD, et al online in The New England Journal of Medicine.

In the trial, 450 patients with venous leg ulcers were randomized in a 1:1 fashion across 20 centers in the United Kingdom to receive either compression therapy and early endovenous ablation (early intervention group, n = 224) or compression therapy alone with consideration for deferred ablation (deferred intervention group, n = 226). In the early intervention group, patients were intended to undergo endovenous saphenous ablation within 2 weeks of randomization. In the deferred intervention group, ablation was considered either after the ulcer had healed or at least 6 months after randomization if it had not.

At Charing Cross, EVRA investigators and trial participants including Dr. Gohel, Francine Heatley, BSc, and David Epstein, PhD, detailed the trial's rationale and methods, means of data collection and analysis, cost-effectiveness parameters, and the trial's context within the health care landscape surrounding venous ulcer disease.

Principal investigator Professor Alun H. Davies, DSc, of London's Imperial College Healthcare presented the trial's main outcomes.

Dr. Gohel and Ms. Heatley each emphasized the significant roles that patients played in the research, including participating in the EVRA steering committee and providing perspectives on which outcomes truly mattered most. Key among these was time to ulcer healing, which became the primary outcome measure in EVRA. Secondary outcomes included ulcer healing rate, ulcer-free time to 1 year, venous clinical severity score, quality of life, and cost-effectiveness.

As detailed by Ms. Heatley, the Clinical Trials Manager at Imperial College, trialists screened a total of 6,555 patients between October 2013 and September 2016, with the 450 randomized patients representing an overall inclusion rate of 7%. The most significant reason for exclusion was ulcer presence exceeding 6 months, which was reported in 1,772 potential participants. Based on demographics and conditions, the arms were described as being well balanced.

Operators could select their preferred means of endovenous ablation, with laser, radiofrequency ablation, foam sclerotherapy, and nonthermal, nontumescent modalities all included in the trial (within some provisos and abiding certain key principles). Analyses of results by treatment modality were not included in the publication or presentation, with the investigators noting that such comparison was not part of the trial; all modalities were said to have performed well. Similarly, participating centers were able to use their preferred established methods for compression therapy and wound care.

Among the key data were a median time of ulcer healing of 56 days in the early intervention group versus 82 days in the deferred intervention group. Patients in the early intervention group also saw higher rates of ulcer healing at 24 weeks: 85.6% for early intervention versus 76.3% in the deferred intervention group (unadjusted Kaplan-Meier time-to-event rates). One year after randomization, 93.8% of patients in the early intervention group exhibited healed ulcers, whereas this rate in the deferred intervention group was 85.8%. The median ulcer-free time in the first year was 306 days in the early intervention group and 278 days in the deferred intervention group.

Prof. Davies noted the high level of compliance in the deferred intervention group, with participants' compression compliance exceeding that seen in previous studies. But the key data were, he emphasized, that the group receiving early intervention fared significantly better in terms of reduced time to healing and increased ulcer-free time. Quality-of-life reports also significantly favored the early intervention group.

Cost-effectiveness analyses presented by Dr. Epstein showed that while the timing of costs varied between the arms, the overall costs were more or less equal.

"Anybody with a potential venous ulcer should have a rapid assessment, and if suitable, should be offered rapid intervention to treat their superficial venous reflux," concluded Prof. Davies, who predicted that the EVRA results would soon affect national guidelines and have global impact as to how people with venous ulcers should be treated. Patient and provider education are now paramount.

Raghu Kolluri, MD, of OhioHealth in Columbus, Ohio, was invited by the Charing Cross organizers to provide commentary on the ramifications of EVRA. Speaking with Endovascular Today after the session, Dr. Kolluri was hopeful that EVRA can be a game-changer and agreed with Prof. Davies' assertion that these results should lead to changes in guidelines regarding the treatment of venous disease.

"EVRA brought the most severe manifestation of venous disease to the forefront, and its publication in The New England Journal of Medicine will hopefully bring more attention to the disease process itself," said Dr. Kolluri. "This is a landmark trial proving that early intervention and ablation of saphenous reflux can lead to improved ulcer healing, decreased recurrence, and more ulcer-free days."