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

NCT ID: NCT03325504

Last Updated: 2024-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-09-05

Study Completion Date

2023-12-15

Brief Summary

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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

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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.

Conditions

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Non Union Fracture

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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hBM-MSCs-Low Dose

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

Group Type EXPERIMENTAL

Cultured Mesenchymal Stem Cells

Intervention Type BIOLOGICAL

Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

hBM-MSCs-High Dose

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

Group Type EXPERIMENTAL

Cultured Mesenchymal Stem Cells

Intervention Type BIOLOGICAL

Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

Autologous iliac crest graft

Autologous Iliac Crest Grafting

Group Type ACTIVE_COMPARATOR

Autologous iliac crest graft

Intervention Type PROCEDURE

Autologous iliac crest grafting

Interventions

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Cultured Mesenchymal Stem Cells

Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

Intervention Type BIOLOGICAL

Autologous iliac crest graft

Autologous iliac crest grafting

Intervention Type PROCEDURE

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

99 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Universidad Autonoma de Madrid

OTHER

Sponsor Role lead

Responsible Party

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Prof Enrique Gomez-Barrena

Full Professor and Chair of orthopaedic surgery

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Enrique Gomez-Barrena, Prof

Role: PRINCIPAL_INVESTIGATOR

Universidad Autonoma de Madrid

Locations

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CHU Clermont-Ferrand

Clermont-Ferrand, , France

Site Status

Department of Orthopaedic Surgery, Hospital Henri Mondor

Créteil, , France

Site Status

Department of Orthopaedic Surgery, CHU Nantes

Nantes, , France

Site Status

Department of Orthopaedic Surgery Toulouse University Hospital

Toulouse, , France

Site Status

Department of Orthopaedic Surgery, CHU Tours

Tours, , France

Site Status

Universitätsklinikum Frankfurt, Department of Trauma, Hand and Reconstructive Surgery

Frankfurt, , Germany

Site Status

Universitätsklinikum Freiburg, Klinik für Orthopädie und Unfallchirurgie

Freiburg im Breisgau, , Germany

Site Status

Universitätsklinikum München

Munich, , Germany

Site Status

Department of Orthopaedic Trauma, University of Ulm

Ulm, , Germany

Site Status

Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa

Bologna, , Italy

Site Status

Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia

Brescia, , Italy

Site Status

Istituto Ortopedico Galeazzi, Chirugia dell´Anca l

Milan, , Italy

Site Status

Hospital U. Puerta de Hierro-Majadahonda, Servicio de Cirugía Ortopédica y Traumatología

Majadahonda, Madrid, Spain

Site Status

Hospital Clínica San Carlos, Servicio de Cirugía Ortopédica y Traumatología

Madrid, , Spain

Site Status

Hospital U. 12 de Octubre, Servicio de Cirugía Ortopédica y Traumatología

Madrid, , Spain

Site Status

Hospital U. Gregorio Marañon, Servicio de Cirugía Ortopédica y Traumatología

Madrid, , Spain

Site Status

Hospital U. La Princesa, Servicio de CirugíaOrtopédica y Traumatología

Madrid, , Spain

Site Status

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Site Status

Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz

Madrid, , Spain

Site Status

Countries

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France Germany Italy Spain

References

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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.

Reference Type BACKGROUND
PMID: 29535772 (View on PubMed)

Related Links

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http://orthounion.eu

Webpage of the Orthounion Study

Other Identifiers

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2015-000431-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EUCTR2015-000431-32-ES

Identifier Type: REGISTRY

Identifier Source: secondary_id

ORTHOUNION

Identifier Type: -

Identifier Source: org_study_id