Abstract
Background
Identification of novel therapeutics to accelerate acute fracture healing remains critical. A prostaglandin EP-2 receptor agonist (CP-533,536) has demonstrated acceleration of fracture healing in preclinical models. The objective of this study is to assess the efficacy of a single dose of CP-533,536 in subjects with a closed fracture of the tibial shaft using radiographic measurements compared to placebo treatment.
Methods
In a phase II randomised, blinded, placebo-controlled trial, the efficacy of a single local injection of three doses of CP-533,536 (0.5mg, 1.5mg and 15mg) was compared to a placebo and a standard of care arm in patients with closed tibial shaft fractures. The tibial fractures were treated with reamed inter-locked intramedullary nails. Patients were followed at two week intervals to six months with a final evaluation at one year. Fracture healing was independently adjudicated by a radiologist panel and an orthopaedic surgeon panel.
Results
Ninety-nine patients were enrolled ranging from 17-76 years in age. Baseline characteristics were comparable across treatment groups. No statistically significant differences in median healing time between any of the CP-533,536 treatment groups and placebo were observed based on the radiology panel assessment; however, significant differences were demonstrated by an orthopaedic panel. At weeks 8, 10, 12, 14 and 16 a higher percentage of subjects in the CP-533,536-1.5 and 0.5 mg groups were considered healed compared to the placebo and the 15 mg groups by the orthopaedic panel assessment. Moreover, the CP-533,536- 0.5 mg group showed a statistically higher (p=0.05) mean radiographic healing score than placebo treated group at weeks 8, 14, 16, 18, and 24.
Conclusion
CP-533,536 demonstrated accelerated healing in patients with acute tibia fractures by an orthopaedic panel. Confirmatory trials are required to assure validity of the observed treatment effects.
