Evaluation of the Clinical Effectiveness of Bioactive Glass (S53P4) in the Treatment of Tibia and Femur Non-unions

Study Overview
=================
Brief Summary
-----------------
Abstract Background: Treatment of non-union remains challenging and often necessitates augmentation of the resulting defect with an autologous bone graft (ABG). ABG is limited in quantity and its harvesting incurs an additional surgical intervention leaving the risk for associated complications and morbidities. Therefore, artificial bone graft substitutes that might replace autologous bone are needed. S53P4-type bioactive glass (BaG) is a promising material which might be used as bone graft substitute due to its osteostimulative, conductive and antimicrobial properties. In this study, the investigators plan to examine the clinical effectiveness of BaG as a bone graft substitute in Masquelet therapy in comparison with present standard Masquelet therapy using an ABG with tricalciumphosphate to fill the bone defect. Methods/design: This randomized controlled, clinical non-inferiority trial will be carried out at the Department of Orthopedics and Traumatology at Heidelberg University. Patients who suffer from tibial or femoral non-unions with a segmental bone defect of 2-5 cm and who are receiving Masquelet treatment will be included in the study. The resulting bone defect will either be filled with autologous bone and tricalciumphosphate (control group, N = 25) or BaG (S53P4) (study group, N = 25). Subsequent to operative therapy, all patients will receive the same standardized follow-up procedures. The primary endpoint of the study is union achieved 1year after surgery. Discussion: The results from the current study will help evaluate the clinical effectiveness of this promising biomaterial in non-union therapy. In addition, this randomized trial will help to identify potential benefits and limitations regarding the use of BaG in Masquelet therapy. Data from the study will increase the knowledge about BaG as a bone graft substitute as well as identify patients possibly benefiting from Masquelet therapy using BaG and those who are more likely to fail, thereby improving the quality of non-union treatment.

Official Title
-----------------
Evaluation of the Clinical Effectiveness of Bioactive Glass (S53P4) in the Treatment of Non-unions of the Tibia and Femur: a Randomized Controlled Non-inferiority Trial

Conditions
-----------------
Pseudoarthrosis of Bone

Intervention / Treatment
-----------------
* Device: bioglass (S53P4)
* Device: RIA and TCP


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: pseudarthrosis of the tibia or femur bone defect < 5 cc surgical treatment with Masquelet technique Exclusion Criteria: age under 18 disagreement patients who require amputation of the affected limb

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Masquelet technique: bioactive glass<br> | Device: bioglass (S53P4)<br>* surgical procedure: Masquelet defect augmentation with bioglass<br>|
| Active Comparator: Masquelet technique: RIA + TCP<br> | Device: RIA and TCP<br>* surgical procedure: Masquelet defect augmentation with RIA and TCP<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of participants with osseus consolidation evaluation via x-ray | x-ray in 2 planes; union = cortical bridging of at least three out of four cortices | 1 year post-operative Masquelet step II | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 12-item Short Form Survey (SF-12) | Quality of life: Physical Score 23.99938(lowest/worst)-56.57706(highest/best), Mental Score 19.06444(lowest/worst)-60.75781 (highest/best) | 1 year post-operative Masquelet step II | 
| Perfusion | Real-time microperfusion assessment using Contrast enhanced ultra-sound (CEUS), contrasting agent: SonoVue. Objective perfusion quantification (using VueBox). Evaluation of characteristic perfusion parameters such as: wash-in rate, wash-in perfusion index | 3 months post-operative Masquelet step II | 
| Rate of participants with osseus consolidation evaluation via CT | union = cortical bridging of at least three out of four cortices | 1 year post-operative Masquelet step II |