The Use of Growth Factors for the Treatment of Chronic Venous Leg Ulcers: A Systematic Review and Meta-Analysis

The objective of this study was to evaluate the impact of growth factors or treatments high in growth factors on patients with lower limb chronic venous leg ulcers (VLUs). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). MEDLINE and Embase up to February 2018 were searched. Studies were eligible for inclusion if they compared a growth factor vs placebo or standard care in patients with VLUs. Two reviewers independently selected RCTs and assessed risk of bias. The primary outcome measure was complete wound healing, and secondary outcomes were percentage reduction in wound area and adverse events. Pooled proportions of patients were calculated using a random-effects model, and heterogeneity among studies was assessed using inconsistency statistic and subgroup analyses. From 1460 studies, we included 12 RCTs (n = 722). RCTs assessed platelets (platelet lysate, platelet gel, platelet-rich growth factor, platelet-rich plasma, platelet-rich fibrin), keratinocyte growth factor 2, endothelial growth factor, transforming growth factor β2, and granulocyte-macrophage colony-stimulating growth factor. There was no significant difference between any growth factor and placebo in complete wound healing (437/722 [59.97%] vs 285/722 [39.47%]; relative risk, 1.34, 95% confidence interval, 0.94-1.90, P = .10; I2 = 71%, 11 trials; low-quality evidence). Subgroup analysis indicated that granulocyte-macrophage colony-stimulating growth factor held a significant increase in the number of wounds completely healed, whereas placebo demonstrated significantly more wounds completely healed compared with keratinocyte growth factor 2. When any growth factor was compared with placebo, there was a significant increase in percentage wound reduction by 48.72% (95% confidence interval, 39.14-58.30; P < .00001; I2 = 0%, four trials; low-quality evidence). There was no significant difference in overall adverse event rate. In patients with chronic VLUs, growth factors have nonsignificant effect in complete wound healing. However, growth factors may increase percentage reduction in wound area. This suggests that additional interventions may be needed to achieve complete wound healing.