Efficacy and Time Sensitivity of Amniotic Membrane treatment in Patients with Diabetic Foot Ulcers: A Systematic Review and Meta-analysis.

Introduction: Diabetic foot ulcers (DFUs) are complex chronic wounds which have a major long-term impact on the morbidity, mortality and quality of patients. The objective of this study was to assess the efficacy and time sensitivity of human amnion/chorion membrane treatment in patients with chronic DFUs.

Methods: The Cochrane Library, PubMed, Embase and Web of Science databases were systematically searched to identify relevant articles up to 10 April 2017. All randomized controlled trials (RCTs) comparing human amnion/chorion membrane + standard therapy and standard therapy alone in patients with DFUs were included in the analysis. Eligible studies were reviewed and data extracted into standard form. The Cochrane Collaboration's tool for assessing the risk of bias was used. Review manager version 5.3 software was used for statistical analysis. Data were analyzed using a random effect model.

Results: Overall, the initial search of the four databases identified 352 published studies; of these, seven RCTS were ultimately included in the meta-analysis. The overall test effect in the group assessed at 4 weeks was Z = 4.14 [P < 0.0001; odds ratio (OR) 0.05; 95% confidence interval (CI) 0.01-0.21]. The overall test effect in the group assessed at 6 weeks was Z = 4.28 (P < 0.0001; OR 0.07; 95% CI 0.02-0.23). The overall effect in the group assessed at 12 weeks was Z = 4.96 (P < 0.00001; OR 0.10; 95% CI 0.04-0.24. The results showed that patients receiving amniotic membrane + standard therapy had far fewer incomplete healing wounds than those receiving standard of care alone. Assessment of the wound healing state at 4 and 6 weeks revealed that the wound healing state was almost the same, but there was a net difference of wound healing state at 12 weeks.

Conclusion: Human amnion/chorion membrane + standard of care treatment heals DFUs significantly faster than standard of care alone. When using the amnion in patients with DFUs, the optimal times to assess progress in wound healing should be 4 and 12 weeks.