Systematic Review: Randomized Controlled Trials Of Protease Modulating Dressings For Treating Diabetic Foot Ulcers

Background:Foot ulceration affects 15% to 20% of people with diabetes. It is a major precursor to amputation in this patient group, early and appropriate treatment can provide the greatest opportunity for healing. Recent research has also explored the role of protease modulating dressings in healing of diabetic foot ulcers. But the evidence of their effectiveness for treating foot ulcers in people with diabetes is generally poor.Objectives:To determine the effects of dressings that modulate the activity of protease on healing of diabetic foot ulcers.Methods:Search methods:We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), Ovid MEDLINE (1950 to October Week 2 2010), Ovid MEDLINE-In-Process & Other Non-Indexed Citations (searched 26 October 2010), Ovid EMBASE (1980 to 2010 Week 42) and EBSCO CINAHL (1982 to 22 October 2010), ICTRP (searched 27 October 2010). The Cochrane Wounds Group Specialised Register also provided data (searched 27 October 2010). There were no restrictions based on language, date or publication status.Select criteria:Randomized controlled trials (RCTs) published and unpublished were included if they evaluate the effects of protease modulating dressings (used singly or in combination with other dressings/agents) on the healing of diabetic foot ulcers. The enrolled participants were type I or type II diabetes with full thickness ulcers of> 4 weeks duration.Data collection and analysis:Two review authors independently identified studies. Data from identified studies were extracted and assessed by two independent review authors. Any disagreement between two reviewers regarding inclusion or exclusion of a study, it was resolved through discussion or by reference to a third reviewer. The third reviewer also assessed rejected studies. If data were missing from reports, original authors were contacted and asked to provide missing information. If no replay, There were classified as’unclear’. The effectiveness and safety were evaluated by in term of proportion of ulcers completely healed at a specified time point, Change in total ulcer area (either absolute or percentage change), Time to complete healing or reduced size, Adverse effects of treatment, Costs. The Review Manager Software version 5.0 was used for analysis. In the presence of heterogeneity a random effects method would be used. Dichotomous outcomes would be reported as risk ratios (RR) with 95%CI. For continuous outcomes, the Mean Difference (MD) with 95%CI have been used.Results: Five RCTs met the inclusion criteria involving 407 participants with diabetic foot ulcers. Results from studies exhibited significant clinical heterogeneity, as characteristics of participants, types of interventions, types of control interventions outcomes measures, outcome assessment methods, duration of follow-up and risk of bias were varied between studies, which were predominantly at unclear or high risk of bias. Thus the results of this systematic review were presented by qualitative synthesis.Oxidized regenerated cellulose/collagen compared with standard wound care:(1) proportion of ulcers completely healed:When data from two trials were pooled, there was no statistically significant between two groups in proportion of ulcers completely healed (RR 0.49,95%CI 0.17 to 1.45). (2) Mean time to complete healing:2 trials reported mean time to complete healing, there were 157 participants enrolled. The weight mean difference between 2 trials was not significant (WMD 4.35,95%CI-20.83 to 29.54), and there was very obvious statistical heterogeneity (P＜0.00001, I2=99%). (3) Percentage change in total ulcer area:Three trials were reported percentage change in total ulcer area. Only one trial presented detail outcomes about this domain, those ulcers treated with ORC/collagen were reported as achieving healing in an average of 26.1±31%, compared with the control group healing in an average of 46.1±27.4%. The remaining trial were only reported the mean value, there was insufficient data presented for standard deviation, the author have been contacted and we are awaiting study data. (4) adverse effects of treatment: Only one trial reported in this domain, there was no difference in safety measurements between two groups. All the adverse events were observed which none related to the dressings and were expected in this category of patient. There was no difference observed in the occurrence of osteomyelitis, infection or cellulitis.ORC/collagen compared with autologous growth factors:(1) Proportion of ulcers completely healed:Complete healing occurred in two patients in each group at the end of the 8 weeks follow-up period. Topical doxycycline 1%gel compared with standardized wound care:(1) Proportion of ulcers completely healed:In the doxycycline treatment group,3/4 (75%) ulcers healed within twenty weeks, compared with 1/3 (33.3%) in the placebo group. RR was 0.42 [95%CI (0.11 to 1.53), P=0.19], no statistically significant difference.Conclusions:There is moderate evidence to suggest that ORC/collagen dressings increases diabetic foot ulcers healing compared with moistened gauze. However there is insufficient evidence to support the use of topical doxycycline hydrogel 1%for treating diabetic foot ulcers. All the enrolled trials are general small and of poor methodologic quality in many case. Although ORC/collagen was shown an effective treatment for diabetic foot ulcers, when applying for clinical practice the results should be viewed with caution specifically. Obviously, these data need to be confirmed in larger, well designed clinical trials.