Efficacy and safety of ornithine alpha-ketoglutarate in heel pressure ulcers in elderly patients: Results of a randomized controlled trial

Pressure ulcers affect predominantly the elderly and nutritional status is a known risk factor. Guidelines on pressure ulcers provide recommendation on nutritional management. Ornithine alpha-ketoglutarate (OKG) is an adjuvant treatment in undernourished elderly patients or in patients with hypercatabolism states. It is a precursor of different amino-acids which play a role in the process of healing. The objective of the study is to determine the efficacy of OKG on pressure ulcer area reduction after six weeks of treatment. Multi-centre, international, randomized, comparative, double blind, parallel groups, placebo-controlled study. 160 patients (ITT population) aged over 60 years with a heel pressure ulcer at stage II or III. Patients received OKG (n=85) or placebo (n=75) once a day for 6 weeks. Ulcer area was measured each week, using a tracer. The primary endpoint was the percentage reduction of the surface at the final visit: [(Wound areatn - Wound areat0)/(Wound areat0)]. At inclusion, ulcer area distribution deviated from normal distribution (median ulcer area OKG 6.6cm(2), placebo 3.9 cm(2), p=0.044, Mann-Whitney test). As healing is strongly related to baseline ulcer area, the abnormal distribution was a major bias. Therefore it was decided to perform the analysis on 2 sub-groups of patients according to the mean ulcer area, i.e. above or below 8cm(2). The mean wound area reduction for baseline area a parts per thousand currency sign 8 cm(2) are -59. 5 +/- 71.4% and -54.0 +/- 69.0% for the OKG group and placebo groups respectively (p=0.477, Mann-Whitney test). In the group with baseline pressure ulcer area > 8 cm(2) no between group differences on either parameter was detected. When closure rate is considered, a significant difference in favor of OKG group is observed (- 0.07 cm(2)/day in the OKG group and - 0.04 cm(2)/day in the placebo groups respectively p=0.007, Mann-Whitney test). Thirty serious adverse events were reported in 28 patients (15 allocated to OKG and 13 to placebo). None of them was considered treatment related. This clinical trial supports a potential benefit of OKG 10g daily in the subgroup of patients with pressure ulcers a parts per thousand currency sign 8 cm(2) surface area in elderly population when associated with debridement together with wound management according to pressure ulcer guidelines. However this study highlights methodological difficulties to perform clinical trials in old-old patients that may affect the robustness of the results for this type of study.