Objectives: To compare the clinical effectiveness and cost-effectiveness of low-dose ultrasound delivered in conjunction with standard care against standard care alone in the treatment of hard-to-heal venous ulcers.
Design: A multicentre, pragmatic, two-armed randomised controlled trial with an economic evaluation.
Setting: Community nurse services; community leg ulcer clinics; hospital outpatient leg ulcer clinics, among both urban and rural settings in England, Scotland, Northern Ireland and Ireland.
Participants: Patients with a venous leg ulcer of > 6 months' duration or > 5 cm2 and an ankle-brachial pressure index of ≥ 0.8. In total, 337 patients were recruited to the study.
Interventions: Participants in the intervention group received low-dose ultrasound (0.5 W/cm2) delivered at 1 MHz, pulsed pattern of 1 : 4, applied to periulcer skin (via a water-based contact gel) weekly for up to 12 weeks alongside standard care. Standard care consisted of low-adherent dressings and compression therapy, renewed as recommended by the patient's nurse and modified if required to reflect changes in ulcer and skin condition. The output of the ultrasound machines was checked every 3 months to confirm intervention fidelity.
Main outcome measures: The primary end point was time to healing of the largest eligible ulcer (reference ulcer). Secondary outcomes were time to healing of all ulcers, proportion of patients healed, percentage and absolute change in ulcer size, proportion of time patients were ulcer free, cost of treatments, health-related quality of life (HRQoL), adverse events, withdrawal and loss to follow-up.
Results: There was a small, and statistically not significant, difference in the median time to complete ulcer healing of all ulcers in favour of standard care [median 328 days, 95% confidence interval (CI) 235 days, inestimable] compared with ultrasound (median 365 days, 95% CI 224 days, inestimable). There was no difference between groups in the proportion of patients with ulcers healed at 12 months (72/168 in ultrasound vs 78/169 standard care), nor in the change in ulcer size at 4 weeks. There was no evidence of a difference in recurrence of healed ulcers. There was no difference in HRQoL [measured using the Short Form questionnaire-12 items (SF-12)] between the two groups. There were more adverse events with ultrasound than with standard care. Ultrasound therapy as an adjuvant to standard care was found not to be a cost-effective treatment when compared with standard care. The mean cost of ultrasound was £197.88 (bias-corrected 95% CI -£35.19 to £420.32) higher than standard care per participant per year. There was a significant relationship between ulcer healing and area and duration at baseline. In addition, those centres with high recruitment rates had the highest healing rates.
Conclusions: Low-dose ultrasound, delivered weekly during dressing changes, added to the package of current best practice (dressings, compression therapy) did not increase ulcer healing rates, affect quality of life (QoL) or reduce recurrence. It was associated with higher costs and more adverse events. There is no evidence that adding low-dose ultrasound to standard care for 'hard-to-heal' ulcers aids healing, improves QoL or reduces recurrence. It increases costs and adverse events. The relationship between ulcer healing rates and patient recruitment is worthy of further study.
Trial registration: Current Controlled Trials ISRCTN21175670.
Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 13. See the HTA programme website for further project information.