Objective: 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.
Design: Multi-centre, international, randomized, comparative, double blind, parallel groups, placebo-controlled study.
Participants: 160 patients (ITT population) aged over 60 years with a heel pressure ulcer at stage II or III.
Intervention: Patients received OKG (n=85) or placebo (n=75) once a day for 6 weeks.
Measurements: 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)].
Results: At inclusion, ulcer area distribution deviated from normal distribution (median ulcer area OKG 6.6 cm(2), placebo 3.9 cm2, 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 8 cm2. The mean wound area reduction for baseline area <or= 8 cm2 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 cm2 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 cm2/day in the OKG group and - 0.04 cm2/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.
Conclusion: This clinical trial supports a potential benefit of OKG 10g daily in the subgroup of patients with pressure ulcers <or= 8 cm2 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.