Wound healing trajectories as predictors of effectiveness of therapeutic agents.

BACKGROUND One goal of wound healing research is to discover agents to accelerate healing. Regulatory agencies have suggested stringent criteria to determine efficacy, that of 100% wound closure. Data analysis at a single point such as 100% closure does not provide detailed information about agent effectiveness over the entire span of healing. HYPOTHESIS Wound healing trajectories can provide such information and can be used to demonstrate utility as alternative end points for wound healing trials. DESIGN Data from 160 patients in 11 clinical trials of diabetic foot ulcers conducted at 2 centers were evaluated. Wound healing trajectories were constructed for patients whose wounds healed (100% closure) and those whose did not (<100% closure) over a 20-week period. The percentage of patients achieving total healing vs time of treatment was plotted and divided into patients receiving a test agent or placebo. RESULTS The healing trajectories were almost identical for patients achieving complete healing at the 2 centers, as were the trajectories for patients with less than 100% closure. However, the trajectories of patients achieving total healing were significantly different from those not achieving 100% closure. Fifty-two percent of all patients achieved 100% healing by 20 weeks; 61% of patients receiving an experimental agent had total healing compared with 39% of placebo-treated patients. Linear regression suggested that all patients would achieve total healing by 37 weeks. CONCLUSIONS Since wound healing trajectories for diabetic foot ulcers treated at 2 centers so closely mimic one another, trajectories might be useful efficacy end points, and used to compare significant points along a continuum rather than a single static end point. Shifting of the wound healing trajectory from an impaired to a more ideal course may be considered when determining efficacy of new wound treatments.