A Prospective Randomized Controlled Trial on the Use of Bone Morphogenetic 7 (BMP-7) (OP-1®) and Demineralized Bone Matrix in Tibial Non-union

Study Overview
=================
Brief Summary
-----------------
The researchers propose a prospective, randomised partially-blinded study to investigate the clinical and radiological outcome, effect on quality of life and socio-economic impact of non-union of diaphysary tibial fractures treated with BMP-7 in adjunct to fresh frozen allograft, in comparison to treatment with allograft together with DBM (demineralised bone matrix).

Official Title
-----------------
A Prospective Randomised Controlled Trial on the Use of BMP-7 (OP-1®) and Demineralised Bone Matrix in Tibial Non-union

Conditions
-----------------
Non-union Diaphysary Tibial Fractures

Intervention / Treatment
-----------------
* Procedure: BMP-7 in adjunct to fresh frozen allograft
* Procedure: allograft together with DBM


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diaphysary tibial non-unions will be included (9 months after first surgery) Major surgery includes exchange nailing, bone grafting, internal fixation, amputation and soft-tissue coverage procedures, such as delayed primary closure and free flaps Surgery is classified as minor for removal of external fixator pins for local infection and removal of a static locking screw from intramedullary nails, a procedure known as dynamization ASA 1 and ASA 2 Gap length/bone contact detected (1-5 cm): largest cortical gap in any radiographic incidence Subject or legal guardian is willing and able to understand, sign and date the study specific Patient Informed Consent, which has been approved by the Institutional Review Board Agrees to participate in post-operative evaluations and required rehabilitation regimen Exclusion Criteria: Patients with known hypersensitivity to the active substance or collagen Gap more than 5 cm Immature skeleton Known auto-immune disease, including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjögren's syndrome and dermatomyositis/polymyositis Active infection on unhealed site or active systemic infection Non-healing resulting from pathological fractures, tumours or metabolic bone diseases Presence of tumour in vicinity of non-union Patients receiving chemotherapy, radiotherapy or immunosuppressant treatment or excessive steroids Patients with severely compromised soft tissue coverage or vascularisation at the non-union site, sufficient to impair bone healing Patients with congenital non-union Pregnancy and lactation Non-union of multiple bones interfering with walking Patients with neuromuscular diseases or conditions interfering normal weight bearing Patients who, judged by the surgeon, are candidates for just internal fixation alone

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 2<br>non-union of diaphysary tibial fractures will be treated with allograft together with DBM | Procedure: allograft together with DBM<br>* non-union of diaphysary tibial fractures treated with allograft together with DBM<br>|
| Experimental: 1<br>non-union of diaphysary tibial fractures will be treated with BMP-7 in adjunct to fresh frozen allograft | Procedure: BMP-7 in adjunct to fresh frozen allograft<br>* non-union of diaphysary tibial fractures treated with BMP-7 in adjunct to fresh frozen allograft<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| X-ray evaluation |  | After 9 months | 
| Change in VAS and LEFS scores |  | After 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of incapacity to work |  | Until ability to work | 
| Change in SF-36 |  | After 4 years | 
| Total socio-economic cost estimation |  | After 4 years | 
| Repeated surgery (minor and major) |  | After 4 years | 
| (Surgical) complications |  | After 4 years | 
| Ability to bear weight (% of body weight) |  | After 4 years |