Randomized, Placebo-controlled Clinical Trial Evaluating Ketotifen Fumarate in Reduction of Post-traumatic Elbow Joint Contracture

Abstract

Grant support received from: American Foundation for Surgery of the Hand There is no financial information to disclose. Post-traumatic joint contractures (PTJC) are a significant complication following intra-articular injuries. Our research has established that a myofibroblast-mast cell-neuropeptide axis underlies the joint capsule fibrosis that limits motion of the human elbow and a rabbit knee model of PTJC.1-3 In our rabbit model, we have established that Ketotifen Fumarate (KF), a mast cell stabilizer, prevents growth factor release and decreased contracture severity by 50% concomitant with decreased measures of fibrosis.2-4 We hypothesized that oral KF would decrease elbow PTJC severity, compared with placebo, in patients with intra-articular elbow fractures and/or dislocations. A randomized, placebo-controlled clinical trial comparing 6-weeks of oral KF 5 mg twice daily to a lactose placebo in patients sustaining distal humerus (AO/OTA 13) and proximal radius +/- ulna (AO/OTA 21) fractures. The primary outcome measure was flexion-extension range of motion (ROM) arc at 12-weeks post-injury. Secondary outcomes included the Disabilities of the Arm, Hand and Shoulder (DASH) score, complication rate, and fracture healing. Statistical analysis consisted of chi-square for categorical variables and ANOVA for continuous variables. Multiple linear regression based on robust estimators was used to assess the adjusted effect of KF. 145 participants were randomized (76 KF, 69 placebo). There were no significant differences between the two groups for baseline characteristics including age, sex, side of injury, hand dominance, pre-injury work status, time to randomization, injury types, and operation; all P > 0.05 (Table 75-1). The 12-week follow up rate was 88% in the KF group and 89% in the placebo group. There was no significant difference between the treatment groups in the primary outcome measure, serious adverse event rates, or (re) operation rates; P > 0.05. But there was a significant difference between operative and non-operative groups on extension-flexion arc of motion (P = 0.03). Fracture healing at the time of analysis found 48% of participants in each group had achieved union. •Patients requiring surgical treatment, as a surrogate for increased injury severity, demonstrated increased PTJC.•The greater loss of motion at 12 weeks in the operative sub-group will inform future Phase III multi-centre injury inclusion criteria to elbow fractures or dislocations requiring surgical treatment.•Several measures of safety were compiled that confirmed the safety of Ketotifen in elbow fractures or dislocations.Table 75-1Baseline CharacteristicsCharacteristicKetotifenPlaceboAge – years, mean (SD)46.7 (18.3)44.4 (13)Sex – female (%)41 (54)29 (42)Side of Injury – right (%)32 (42)26 (38)Hand dominance – right (%)63 (83)56 (81)Work status – employed (%)56 (74)52 (75)Injury to randomization – days, mean (SD)3.7 (2.1)3.7 (2.1)Injury Fracture Type 13 (distal humerus): Type 21 (proximal radius +/- ulna)11:517:48Injury Dislocation Posterior1212Operation – yes (%)34 (45)31 (45) Open table in a new tab This research was supported by a 2012 Clinical Research Grant from the American Foundation for Surgery of the Hand.