A Comparative Study of 2 Doses of BM Autologous H-MSC+Biomaterial vs Iliac Crest AutoGraft for Bone Healing in Non-Union (ORTHOUNION)

Universidad Autonoma de Madrid

Status and phase: Completed; Phase 3

Conditions: Non Union Fracture

Treatments: Procedure: Autologous iliac crest graft; Biological: Cultured Mesenchymal Stem Cells

Study type: Interventional

Funder types: Other

Identifiers

NCT03325504

ORTHOUNION

EUCTR2015-000431-32-ES (Registry Identifier)

2015-000431-32 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 46 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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46 participants in 3 patient groups

hBM-MSCs-Low Dose

Experimental group

Description:

Autologous Cultured Mesenchymal Stem Cells +Biomaterial (Low Dose): 100x106 cells

Treatment:

Biological: Cultured Mesenchymal Stem Cells

hBM-MSCs-High Dose

Experimental group

Description:

Autologous Cultured Mesenchymal Stem Cells+Biomaterial (High Dose): 200x106 cells

Treatment:

Biological: Cultured Mesenchymal Stem Cells

Autologous iliac crest graft

Active Comparator group

Description:

Autologous Iliac Crest Grafting

Treatment:

Procedure: Autologous iliac crest graft