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

Non Union Fracture Clinical Trial

— ORTHOUNION  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03325504
• Other study ID #: ORTHOUNION
• Secondary ID: 2015-000431-32EU
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: September 5, 2017
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2022
• Source: Universidad Autonoma de Madrid
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 46
• Est. completion date: December 31, 2023
• Est. primary completion date: December 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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)

Related Conditions & MeSH terms

• Fractures, Ununited
• Non Union Fracture

Intervention

Biological:
• Cultured Mesenchymal Stem Cells
Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

Procedure:
• Autologous iliac crest graft
Autologous iliac crest grafting

Locations

Country	Name	City	State
France	CHU Clermont-Ferrand	Clermont-Ferrand
France	Department of Orthopaedic Surgery, Hospital Henri Mondor	Créteil
France	Department of Orthopaedic Surgery, CHU Nantes	Nantes
France	Department of Orthopaedic Surgery Toulouse University Hospital	Toulouse
France	Department of Orthopaedic Surgery, CHU Tours	Tours
Germany	Universitätsklinikum Frankfurt, Department of Trauma, Hand and Reconstructive Surgery	Frankfurt
Germany	Universitätsklinikum Freiburg, Klinik für Orthopädie und Unfallchirurgie	Freiburg
Germany	Universitätsklinikum München	Munich
Germany	Department of Orthopaedic Trauma, University of Ulm	Ulm
Italy	Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa	Bologna
Italy	Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia	Brescia
Italy	Istituto Ortopedico Galeazzi, Chirugia dell´Anca l	Milano
Spain	Hospital Clínica San Carlos, Servicio de Cirugía Ortopédica y Traumatología	Madrid
Spain	Hospital U. 12 de Octubre, Servicio de Cirugía Ortopédica y Traumatología	Madrid
Spain	Hospital U. Gregorio Marañon, Servicio de Cirugía Ortopédica y Traumatología	Madrid
Spain	Hospital U. La Princesa, Servicio de CirugíaOrtopédica y Traumatología	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Servicio de Cirugía Ortopédica y Traumatología "A", Hospital La Paz	Madrid
Spain	Hospital U. Puerta de Hierro-Majadahonda, Servicio de Cirugía Ortopédica y Traumatología	Majadahonda	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Universidad Autonoma de Madrid

Countries where clinical trial is conducted

France,  Germany,  Italy,  Spain, 

References & Publications (1)

Gómez-Barrena E, Padilla-Eguiluz NG, Avendaño-Solá C, Payares-Herrera C, Velasco-Iglesias A, Torres F, Rosset P, Gebhard F, Baldini N, Rubio-Suarez JC, García-Rey E, Cordero-Ampuero J, Vaquero-Martin J, Chana F, Marco F, García-Coiradas J, Caba-Dessoux P, de la Cuadra P, Hernigou P, Flouzat-Lachaniette CH, Gouin F, Mainard D, Laffosse JM, Kalbitz M, Marzi I, Südkamp N, Stöckle 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Bone consolidation	The percentage of bone consolidation in the comparator treatment arm ( iliac crest autograft) and experimental treatment arm (mesenchymal cells).	12 months after treatment
Secondary	Bone consolidation	To compare bone consolidation between the experimental arms and the comparator	6 and 24 months
Secondary	Radiological Bone consolidation	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.	6, 12 and 24 months
Secondary	Level of Pain	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.	6, 12 and 24 months
Secondary	Complications	To compare the rate of complications between the experimental arms and the comparator	6, 12 and 24 months
Secondary	Health status	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.	6, 12 and 24 months

External Links

•   Webpage of the Orthounion Study