3 Clinical evidence

Summary of clinical evidence

3.1 The main outcome measures for the promotion of wound healing using the MIST Therapy system are rate of healing and percentage of wounds healed. Also relevant are wound size, wound volume, wound area, level of bacterial contamination (bioburden), treatment time, pain score, quality of life, recurrence and adverse events.

3.2 The manufacturer's submission described almost 200 reports on the clinical use of the MIST Therapy system. The External Assessment Centre considered that ten studies (two randomised controlled trials and eight peer-reviewed observational studies, of which two were prospective) were the key sources of evidence in the evaluation of the clinical effectiveness of the MIST Therapy system.

3.3 In one randomised controlled trial, 70 patients with non-healing wounds and chronic critical limb ischaemia had standard wound care and treatment with the MIST Therapy system (intervention group, n = 35) or standard wound care alone (control group, n = 35) for 12 weeks (Kavros et al. 2007). The MIST Therapy system was used for 5 minutes per treatment, three times per week. Standard wound care included daily dressing changes and weekly wound debridement. The study reported that 63% of wounds healed (healing defined as a greater than 50% reduction in wound volume) in the intervention group compared with 29% in the control group (p < 0.01).

3.4 In the second randomised controlled trial, 133 patients with diabetes and chronic foot ulcers were treated using the MIST Therapy system (intervention group, n = 70) or a sham device (control group, n = 63) for 10 weeks (Ennis et al. 2005). Wounds were treated three times per week, with 4 minutes use of the active or sham device, in addition to standard wound care with dressings and weekly debridement as needed. The study reported that, based on the intention-to-treat analysis, 26% of wounds healed in the intervention group compared with 22% in the control group (not statistically significant).

3.5 The one prospective observational study of 23 patients with chronic lower-extremity wounds of any aetiology treated by the MIST Therapy system (the intervention group) reported that 69% of wounds healed with a mean healing time of 8 weeks (median 7 weeks) (Ennis et al. 2006). These were compared with 218 patients with chronic wounds treated previously by electrical stimulation or megahertz ultrasound (the historical control group) in whom 72% of wounds healed with a mean healing time of 18.7 weeks (median 10 weeks) (p = 0.0005 in favour of the MIST group). The proportion of patients in the historical control group admitted to hospital for wound treatment (including surgical procedures) was significantly higher than in the MIST group (p = 0.04). The MIST Therapy system was used for 3–12 minutes per treatment depending on the area of the wound, three times per week. All patients received standard wound care including daily dressing changes and weekly wound debridement. Patient demographics and wound aetiologies were comparable between the intervention group and the historical control group.

3.6 A retrospective analysis reviewed the medical charts of patients with chronic lower-extremity wounds of any aetiology who were treated using the MIST Therapy system and standard wound care for 90 days (intervention group, n = 163) or standard wound care alone (control group, n = 47) (Kavros et al. 2008). The MIST Therapy system was used for 3–12 minutes per treatment depending on the area of the wound, three times per week. Standard wound care included advanced wound care dressings (silver, collagens) and debridement. The study reported that 53% of wounds healed in the intervention group with a mean healing time of 147 days compared with 32% in the control group, which had a mean healing time of 134 days (p = 0.009). At the start of treatment, the median wound volume in the intervention group and the control group was 304 mm3 and 368 mm3 respectively. The median wound volume in both groups decreased during treatment to a final volume of 0 mm3 in the intervention group and 68 mm3 in the control group.

3.7 A retrospective case series analysed the medical records of 51 patients with chronic lower-extremity ulcers that had been present for 3–18 months. Patients had standard wound care for a mean of 9.8 ± 5.5 weeks followed by the MIST Therapy system for a mean of 5.5 ± 2.8 weeks (Kavros and Schenk 2007). Patients received treatment using the MIST Therapy system when their wounds failed to improve with standard wound care alone and were treated three to five times a week (duration of each treatment was not stated). Standard wound care comprised moist wound dressings, debridement and compression. The study reported a 94.9 ± 9.8% reduction in wound volume during the period with the MIST Therapy system compared with a 37.3 ± 18.6% reduction during the period with standard wound care alone (p < 0.0001). No wound closed using standard wound care alone compared with 26 out of 51 wounds closing (51%) during treatment with the MIST Therapy system.

3.8 One retrospective observational study reviewed the medical charts of 76 patients with non-healing wounds of any aetiology who were treated using the MIST Therapy system as an adjunct to standard wound care (Bell and Cavorsi 2008). Treatment was administered for a mean of 5.1 minutes per treatment for a mean of 2.3 times per week. The median duration of treatment was 4.3 weeks. Standard wound care included moist wound dressings, selective debridement and compression. The study reported that the median wound area was reduced by 79% (from 2.5 to 0.6 cm²) and the proportion of patients with greater than 75% healthy granulation tissue increased from 32% to 46% during treatment. The patient-reported mean pain rating (0–10; a higher score indicates more-intense pain) decreased by a mean of 1.8 points during treatment (p = 0.001).

3.9 Cole et al. (2009) described a retrospective observational study that reviewed the medical charts of 41 consecutive patients with non-healing wounds of any aetiology who were treated using the MIST Therapy system as an adjunct to standard wound care. Treatment was administered for a mean of 3.7 minutes per treatment for a mean of 2.5 times per week. Standard wound care included moist wound dressings, debridement and other interventions specific to wound aetiology. Mean wound area decreased by 60% (median 88%) and the proportion of patients with greater than 75% healthy granulation tissue increased from 26% (n = 12) to 80% (n = 41) during treatment. The percentage of wounds that healed completely was 38% (n = 20) with a mean healing time of 6.8 weeks. The patient-reported mean pain rating (0–10; a higher score indicates more-intense pain) decreased by a mean of 2.9 points during treatment (p < 0.0001).

3.10 Haan et al. (2009) described a retrospective review of medical charts from 48 consecutive patients who had a chronic wound of any aetiology treated using the MIST Therapy system and physical therapy wound management (including debridement, wound dressings, compression, negative-pressure wound therapy and pulsed lavage with suction). Treatment was administered for a mean of 4.1 minutes per treatment for a mean of 2.1 times per week. The review reported that the median wound area decreased by 92% and the proportion of patients with greater than 75% healthy granulation tissue increased from 37% (n = 18) to 89% (n = 41) during treatment (p < 0.0001). The percentage of wounds that healed completely was 24% (n = 12) with a mean healing time of 4.3 weeks. The patient-reported mean pain rating (0–10; a higher score indicates more-intense pain) (n = 42) decreased by a mean of 2.6 (3.6–0.8) points during treatment (p < 0.0001).

3.11 A retrospective case study of medical records from 15 consecutive patients with painful, chronic lower-extremity wounds of various aetiologies treated by the MIST Therapy system reported a decrease in mean pain score (0–10; a higher score indicates more-intense pain) of 6.4 points (8.07 ± 1.91 to 1.67 ± 1.76, p = 0.0003), which was an 80% reduction in patient-reported pain (Gehling et al. 2007). Patients reduced or stopped their use of pain killers within 2 weeks of starting treatment.

3.12 A prospective case series of 11 consecutive patients with chronic pressure ulcers reported bacterial colony counts in the chronic wounds (Serena et al. 2009). Treatment was administered for a mean duration of 4 minutes per treatment, three times a week. No antiseptics, antibiotics, silver or antimicrobial dressings were used during the study. The study reported that the mean wound bioburden decreased by 50% (from 4 x 107 to 2 x 107 colony-forming units per gram of tissue) during treatment. Mean wound area decreased by 26% and mean wound volume decreased by 20% during the treatment period.

Committee considerations

3.13 The Committee considered that the evidence suggested real potential for the MIST Therapy system to enhance the healing of chronic wounds, but that overall the quality of the evidence was limited by small patient numbers and lack of appropriate comparison groups.

3.14 The Committee noted that there was only one study comparing the MIST Therapy system and a sham device for the treatment of chronic wounds and judged the study to be of low quality. In addition to more clinical studies, the Committee considered that it would be useful to have more proof-of-concept evidence to demonstrate the transmission of ultrasound energy through a saline mist.

3.15 The Committee recognised that the quality of evidence in the area of wound care is generally low and that the heterogeneity of chronic wounds poses a challenge. The Committee was advised that the evidence supporting the clinical effectiveness of the MIST Therapy system was equal to or better than evidence for many other wound care interventions in current use in the NHS.

3.16 The Committee noted that patients reported a reduction in pain and an improvement in health following MIST Therapy treatment. It was advised that even partial healing can result in reduction in pain and improvement in quality of life for some patients with chronic wounds.

3.17 The Committee noted limited evidence on the rates of recurrence of chronic ulcers after MIST Therapy treatment. Further information on this longer-term outcome would be useful.

3.18 The Committee noted that no adverse events specific to the use of the MIST Therapy system have been reported in the published literature or to the manufacturer.

3.19 The few available studies on use of the MIST Therapy system for acute wounds were small and lacking in statistical outcomes. The Committee considered there was no substantial evidence to make a judgement on the clinical effectiveness of the MIST Therapy system for the treatment of acute wounds.

  • National Institute for Health and Care Excellence (NICE)