Non Union Fracture
Conditions
Keywords
Non-union, Advanced therapies, Mesenchymal stem cells, Long bone
Brief summary
ORTHOUNION is a multi-centre, open, comparative, randomized, clinical trial with three parallel arms that aims to compare the efficacy of three treatments to enhance bone healing in patients with long bone non-union.
Detailed description
Bone injuries represent an important world medical problem producing significant healthcare and societal expenditure. While most bone injuries are not severe and are capable of healing through bone regeneration by natural callus formation with standard treatments, severe bone injuries may not heal, becoming an important unmet clinical need. Non-unions, or pseudarthrosis, may occur in 5% to 20% of long-bone fractures that fail to heal properly after more than 6 months, with morbidity, prolonged hospitalization, and increased expenses. The most commonly accepted standard augmentation to procure fracture and non-union healing consists of autologous bone grafting, obtained from the same patient in a different surgical site and transplanted to the reconstruction site. However, autologous bone grafting has some drawbacks (such as persistent pain, scar, late recovery, limited amount of bone, etc) and a limited regeneration efficacy (success rate of about 74%) and high societal cost. Culture-expanded autologous MSCs combined with biphasic calcium phosphate (BCP) biomaterial granules have been claimed as a solid regenerative medicine alternative to autologous bone grafting in non-unions, although current data are limited. In this context, the ORTHOUNION initiative focuses on the opportunity to test the hypothesis of superiority of MSC, the investigational ATMP, versus the currently accepted standard therapy, iliac crest bone autograft to biologically augment surgical treatment of long-bone non-unions.
Interventions
BIOLOGICALCultured Mesenchymal Stem Cells
Cultured Mesenchymal Stem Cells obtained from expanded bone marrow
PROCEDUREAutologous iliac crest graft
Autologous iliac crest grafting
Sponsors
Universidad Autonoma de Madrid
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 years and older, both sexes 2. Traumatic isolated closed or open Gustilo I and II, IIIA and IIIB humerus, tibial or femur diaphyseal or metaphysodiaphyseal fracture with a status of atrophic, oligotrophic or normotrophic non-union. 3. Able to understand, accept and sign informed consent 4. Medical health coverage 5. Able to understand and accept the study constraints
Exclusion criteria
1. Hypertrophic non-unions 2. Segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc) 3. Unrecovered vascular or neural injury 4. Other fractures causing interference with weight bearing 5. Visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.) 6. Active infection of any location and aetiology 7. Surgical contraindication of any cause 8. Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control. 9. Malignant tumour (past history or concurrent disease)(except carcinoma in situ or basalioma in remission) 10. History of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection 11. Insulin dependent diabetes 12. Any evidence (confirmed by PCR) of active infection with HIV, Hepatitis B or Hepatitis C infection 13. Any evidence of Syphilis 14. Known allergies to products involved in the production process of MSC 15. Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion 16. Autoimmune inflammatory disease 17. Current treatment by biphosphonates not stopped three months prior to study inclusion 18. Impossibility to meet at the appointments for the follow up 19. Participation in another therapeutic trial in the previous 3 months 20. Second non-union in case of bilateral or multiple non-unions (only one non-union per patient will be included in the trial)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone consolidation | 12 months after treatment | The percentage of bone consolidation in the comparator treatment arm ( iliac crest autograft) and experimental treatment arm (mesenchymal cells). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bone consolidation | 6 and 24 months | To compare bone consolidation between the experimental arms and the comparator |
| Radiological Bone consolidation | 6, 12 and 24 months | To compare bone consolidation, using the REBORNE scale, between the experimental arms and the comparator. The REBORNE scale is an ad-hoc and validated scale, developed by Gomez-Barrena et al. (article currently under preparation) as a modification of the RUST score (Whelan, 2010; Journal of Trauma). In the REBORNE scale, the presence/absence of radiological consolidation is evaluated on a total of 4 cortices. Score range from 0 (no bone callus visible) to 4 (callus present with same density as cortical). The total score will be recorded. |
| Level of Pain | 6, 12 and 24 months | To compare level of pain (by Numeric Rating Scale \[NRS\]) between the experimental arms and the comparator. The NRS is a scale that rates the patient´s pain from 0-10 (0= no pain, 10= worst pain), at the time of the visit. |
| Complications | 6, 12 and 24 months | To compare the rate of complications between the experimental arms and the comparator |
| Health status | 6, 12 and 24 months | To compare the health status (by using the Short Form-36 Health Questionnaire) between treatment arms. The SF-36 questionnaire is a validated, widely used patient-reported health survey which measures their physical and mental health status. It consists of 36 questions organized in 8 dimensions. The total score will be recorded. |
Countries
France, Germany, Italy, Spain
Outcome results
None listed