Clinical trial NCT03325504: A Comparative Study of 2 Doses of BM Autologous H-MSC+Biomaterial vs Iliac Crest AutoGraft for Bone Healing in Non-Union
Official title: A Multi-centre, Open-label, Randomized, Comparative Clinical Trial of Two Doses of Bone Marrow Autologous MSC+ Biomaterial vs Iliac Crest Autologous Graft, for Bone Healing in Non-union After Long Bone Fractures
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Union Fracture
Keywords: Non-union
Advanced therapies
Mesenchymal stem cells
Long bone
Lead sponsor: Universidad Autonoma de Madrid
Sponsor class: OTHER
First posted: 2017-10-30
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Bone consolidation
timeFrame: 12 months after treatment
Secondary outcomes:
measure: Bone consolidation
timeFrame: 6 and 24 months
measure: Radiological Bone consolidation
timeFrame: 6, 12 and 24 months
measure: Level of Pain
timeFrame: 6, 12 and 24 months
measure: Complications
timeFrame: 6, 12 and 24 months
measure: Health status
timeFrame: 6, 12 and 24 months
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU Clermont-Ferrand
city: Créteil
country: France
facility: Department of Orthopaedic Surgery, Hospital Henri Mondor
city: Nantes
country: France
facility: Department of Orthopaedic Surgery, CHU Nantes
city: Toulouse
country: France
facility: Department of Orthopaedic Surgery Toulouse University Hospital
city: Tours
country: France
facility: Department of Orthopaedic Surgery, CHU Tours
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt, Department of Trauma, Hand and Reconstructive Surgery
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg, Klinik für Orthopädie und Unfallchirurgie
city: Munich
country: Germany
facility: Universitätsklinikum München
city: Ulm
country: Germany
facility: Department of Orthopaedic Trauma, University of Ulm
city: Bologna
country: Italy
facility: Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa
city: Brescia
country: Italy
facility: Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia
city: Milano
country: Italy
facility: Istituto Ortopedico Galeazzi, Chirugia dell´Anca l
city: Majadahonda
country: Spain
facility: Hospital U. Puerta de Hierro-Majadahonda, Servicio de Cirugía Ortopédica y Traumatología
state: Madrid
city: Madrid
country: Spain
facility: Hospital Clínica San Carlos, Servicio de Cirugía Ortopédica y Traumatología
city: Madrid
country: Spain
facility: Hospital U. 12 de Octubre, Servicio de Cirugía Ortopédica y Traumatología
city: Madrid
country: Spain
facility: Hospital U. Gregorio Marañon, Servicio de Cirugía Ortopédica y Traumatología
city: Madrid
country: Spain
facility: Hospital U. La Princesa, Servicio de CirugíaOrtopédica y Traumatología
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz
Study officials:
affiliation: Universidad Autonoma de Madrid
name: Enrique Gomez-Barrena, Prof
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gomez-Barrena E, Padilla-Eguiluz NG, Avendano-Sola C, Payares-Herrera C, Velasco-Iglesias A, Torres F, Rosset P, Gebhard F, Baldini N, Rubio-Suarez JC, Garcia-Rey E, Cordero-Ampuero J, Vaquero-Martin J, Chana F, Marco F, Garcia-Coiradas J, Caba-Dessoux P, de la Cuadra P, Hernigou P, Flouzat-Lachaniette CH, Gouin F, Mainard D, Laffosse JM, Kalbitz M, Marzi I, Sudkamp N, Stockle U, Ciapetti G, Donati DM, Zagra L, Pazzaglia U, Zarattini G, Capanna R, Catani F. A Multicentric, Open-Label, Randomized, Comparative Clinical Trial of Two Different Doses of Expanded hBM-MSCs Plus Biomaterial versus Iliac Crest Autograft, for Bone Healing in Nonunions after Long Bone Fractures: Study Protocol. Stem Cells Int. 2018 Feb 22;2018:6025918. doi: 10.1155/2018/6025918. eCollection 2018.