Drugs Xagena
In a clinical study ( study 400 ) the use of InductOs ( Dibotermin alfa ) in acute open tibia fractures, as an adjunct to standard of care ( SOC ), using reamed intramedullary nails, has resulted in a higher number of localised cases of infections in the affected limb than standard of care alone.
The study was specifically designed to assess efficacy and safety of the use of InductOs with reamed intramedullary nail fixation. An increased rate of infection was observed in the InductOs-treated group versus the control group ( 19% versus 9%, respectively ).
The use of reamed nails in combination with InductOs is therefore not recommended and the indication of InductOs is changed accordingly.
Further information on the safety concern
Study 400 ( study 3100N8-400-WW ) is a phase IV single blind study of InductOs conducted as a post-marketing commitment to the EMEA, to assess the efficacy and safety of InductOs with reamed intramedullary nail fixation in subjects with open diaphyseal tibia fractures. Study 400 was conducted to detect if there was a difference in the rate of fracture healing for subjects receiving reamed IM nails with InductOs, compared to standard of care without InductOs. Study 400 was undertaken to verify the efficacy of InductOs reported in the reamed nail patient subgroup of the study submitted with the initial Marketing Authorisation application. Efficacy data are not currently available for study 400.
In study 400, in which the intramedullary canal was reamed to cortical chatter, an increased rate of infection was observed in the InductOs-treated group versus the standard of care group ( 19% versus 9%, respectively ).
Study 400 was not designed to provide new information on the efficacy and safety of InductOs or standard of cure with unreamed nails.
Other than study 400 there is no evidence from clinical trials to confirm that the incidence of infection is lower when using unreamed or reamed nail fixation with InductOs or standard of cure alone.
On the basis of the findings of study 400 the following revisions to the Summary of Product Characteristics have been made.
Therapeutic indications
InductOs is indicated for the treatment o acute tibia fractures in adults, as an adjunct to standard care using open fracture reduction and intramedullary unreamed nail fixation.
Special warnings and precautions for use
Efficacy infomation in tibia fracture is available only from controlled clinical trials in which open tibial fractures were treated using intramedullary nail fixation. In a clinical study in which the intramedullary canal was reamed to cortical chatte, an increased rate of infection was observed in the InductOs-treated group versus the standard of care control group. The use of InductOs with reamed nails in open tibial fracture repair is not recommended.
Undesirable effects
The undesirable effects observed in long bone fracture patients were generally representative of the morbidity associated with either orthopaedic trauma or the surgical process.
Localised infection specific to the fractured limb occurred in greater than or equal to 1/10 patients in a clinical study in which the intramedullary canal was reamed to cortical chatter An increased rate of infection was observed in the InductOs-treated group versus the standard of care control group ( 19% versus 9%, respectively ). For use with unreamed nails, estimated rates of infection were similar between treatment groups in a study ( 21% versus 23%, respectively ).
Pharmacodynamic properties
Treatment with InductOs 1.5 mg/ml was significantly effective in all fracture classes, including severe Gustilo IIIB fractures ( 52% reduced risk of secondary interventions as compared to standard-care patients ).
Source: Medicines and Healthcare product Regulatory Agency MHRA, 2008
XagenaMedicine_2008
