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CompletedNCT03325504ORTHOUNIONUpdated Dec 4, 2024

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

A Phase 3 interventional study of Cultured Mesenchymal Stem Cells and Autologous iliac crest graft in Non Union Fracture, sponsored by Universidad Autonoma de Madrid. Completed at 19 sites in 4 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2024-12-04.

Sponsored by Universidad Autonoma de Madrid · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
18 Years to 99 Years
Sex
All
01

Study 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.

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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.

02

Conditions studied

  • Non Union Fracture

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Keywords

  • Non-union
  • Advanced therapies
  • Mesenchymal stem cells
  • Long bone
03

Who can participate

Ages eligible
18 Years to 99 Years
Sexes eligible
All
Accepts 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

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)
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
46 participants (actual)

Study arms

  • Experimental
    hBM-MSCs-Low Dose

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

    Biological: Cultured Mesenchymal Stem Cells

  • Experimental
    hBM-MSCs-High Dose

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

    Biological: Cultured Mesenchymal Stem Cells

  • Active comparator
    Autologous iliac crest graft

    Autologous Iliac Crest Grafting

    Procedure: Autologous iliac crest graft

Interventions

  • BiologicalCultured Mesenchymal Stem Cells

    Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

  • ProcedureAutologous iliac crest graft

    Autologous iliac crest grafting

05

What researchers measure

Primary outcomes

  1. Bone consolidation

    The percentage of bone consolidation in the comparator treatment arm ( iliac crest autograft) and experimental treatment arm (mesenchymal cells).

    Time frame: 12 months after treatment

Secondary outcomes

  1. Bone consolidation

    To compare bone consolidation between the experimental arms and the comparator

    Time frame: 6 and 24 months

  2. 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.

    Time frame: 6, 12 and 24 months

  3. 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.

    Time frame: 6, 12 and 24 months

  4. Complications

    To compare the rate of complications between the experimental arms and the comparator

    Time frame: 6, 12 and 24 months

  5. 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.

    Time frame: 6, 12 and 24 months

06

Study locations

19 sites
  • 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, 37044, France
  • 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, 8907581, Germany
  • Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa
    Bologna, 40136, Italy
  • Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia
    Brescia, Italy
  • Istituto Ortopedico Galeazzi, Chirugia dell´Anca l
    Milano, Italy
  • Hospital U. Puerta de Hierro-Majadahonda, Servicio de Cirugía Ortopédica y Traumatología
    Majadahonda, Madrid, 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
07

References and documents

Publications

  • 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. PubMed 29535772 ↗
08

Registry details

Key details

Study ID
NCT03325504
Lead sponsor
Universidad Autonoma de Madrid
Responsible party
Prof Enrique Gomez-Barrena (Full Professor and Chair of orthopaedic surgery, Universidad Autonoma de Madrid) — Principal investigator
First posted
Oct 30, 2017
Start date
Sep 5, 2017
Primary completion
Oct 17, 2022
Completion
Dec 15, 2023
Last update
Dec 4, 2024

Study contacts

Enrique Gomez-Barrena, Prof
principal investigator · Universidad Autonoma de Madrid

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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