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Trial record 1 of 1 for:    NCT03325504
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A Comparative Study of 2 Doses of BM Autologous H-MSC+Biomaterial vs Iliac Crest AutoGraft for Bone Healing in Non-Union (ORTHOUNION)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03325504
Recruitment Status : Recruiting
First Posted : October 30, 2017
Last Update Posted : September 20, 2019
Information provided by (Responsible Party):
Prof Enrique Gomez-Barrena, Universidad Autonoma de Madrid

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.

Condition or disease Intervention/treatment Phase
Non Union Fracture Biological: Cultured Mesenchymal Stem Cells Procedure: Autologous iliac crest graft Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 5, 2017
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 30, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Fractures

Arm Intervention/treatment
Experimental: hBM-MSCs-Low Dose
Autologous Cultured Mesenchymal Stem Cells +Biomaterial (Low Dose): 100x106 cells
Biological: Cultured Mesenchymal Stem Cells
Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

Experimental: hBM-MSCs-High Dose
Autologous Cultured Mesenchymal Stem Cells+Biomaterial (High Dose): 200x106 cells
Biological: Cultured Mesenchymal Stem Cells
Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

Active Comparator: Autologous Illiac crest graft
Autologous Iliac Crest Grafting
Procedure: Autologous iliac crest graft
Autologous iliac crest grafting

Primary Outcome Measures :
  1. Bone consolidation [ Time Frame: 12 months after treatment ]
    The percentage of bone consolidation in the comparator treatment arm ( iliac crest autograft) and experimental treatment arm (mesenchymal cells).

Secondary Outcome Measures :
  1. Bone consolidation [ Time Frame: 6 and 24 months ]
    To compare bone consolidation between the experimental arms and the comparator

  2. Radiological Bone consolidation [ Time Frame: 6, 12 and 24 months ]

    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.

  3. Level of Pain [ Time Frame: 6, 12 and 24 months ]

    To compare level of pain (by Numeric Rating Scale [NSR]) 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.

  4. Complications [ Time Frame: 6, 12 and 24 months ]
    To compare the rate of complications between the experimental arms and the comparator

  5. Health status [ Time Frame: 6, 12 and 24 months ]

    To compare the health status (by using the Short Form-36 Health Questionnarie) 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 99 Years   (Adult, Older Adult)
Sexes Eligible for Study:   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:

  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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03325504

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Contact: Enrique Gomez-Barrena, Prof +34912071204
Contact: Cristina Avendano-Sola, MD +34911916479

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Sponsors and Collaborators
Universidad Autonoma de Madrid
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Principal Investigator: Enrique Gomez-Barrena, Prof UAM
Additional Information:
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Responsible Party: Prof Enrique Gomez-Barrena, Full Professor and Chair of orthopaedic surgery, Universidad Autonoma de Madrid Identifier: NCT03325504    
Other Study ID Numbers: ORTHOUNION
2015-000431-32 ( EudraCT Number )
EUCTR2015-000431-32-ES ( Registry Identifier: International Clinical Trials Registry Plataform )
First Posted: October 30, 2017    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof Enrique Gomez-Barrena, Universidad Autonoma de Madrid:
Advanced therapies
Mesenchymal stem cells
Long bone
Additional relevant MeSH terms:
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Fractures, Ununited
Fractures, Bone
Wounds and Injuries