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Non Union FracturePhase 3ORTHOUNIONNCT03325504

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 study testing Cultured Mesenchymal Stem Cells and Autologous iliac crest graft in people with Non Union Fracture, run by Universidad Autonoma de Madrid at 19 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Non Union Fracture
What is being tested?
Cultured Mesenchymal Stem Cells and Autologous iliac crest graft
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
19 sitesin 4 countries
Study dates
5 Sep 2017to 15 Dec 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 years and older, both sexes
  • 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.
  • Able to understand, accept and sign informed consent
  • Medical health coverage
  • Able to understand and accept the study constraints

Who cannot join

  • Hypertrophic non-unions
  • Segmental bone loss requiring specific therapy (bone transport, vascularized graft, large structural allograft, megaprosthesis, etc)
  • Unrecovered vascular or neural injury
  • Other fractures causing interference with weight bearing
  • Visceral injuries or diseases interfering with callus formation (severe cranioencephalic trauma, etc.)
  • Active infection of any location and aetiology
Show all 20Show fewer
  • Surgical contraindication of any cause
  • Pregnancy, breast feeding women and women who are of childbearing age and not practicing adequate birth control.
  • Malignant tumour (past history or concurrent disease)(except carcinoma in situ or basalioma in remission)
  • History of bone harvesting on iliac crest contraindicating new iliac crest bone graft harvesting or bone marrow collection
  • Insulin dependent diabetes
  • Any evidence (confirmed by PCR) of active infection with HIV, Hepatitis B or Hepatitis C infection
  • Any evidence of Syphilis
  • Known allergies to products involved in the production process of MSC
  • Corticoid or immunosuppressive therapy more than one week in the three months prior to study inclusion
  • Autoimmune inflammatory disease
  • Current treatment by biphosphonates not stopped three months prior to study inclusion
  • Impossibility to meet at the appointments for the follow up
  • Participation in another therapeutic trial in the previous 3 months
  • Second non-union in case of bilateral or multiple non-unions (only one non-union per patient will be included in the trial)

Trial locations and contacts

19 sites in 4 countries.

19 sites in 4 countries

Spain7 sites

  • Hospital Clínica San Carlos, Servicio de Cirugía Ortopédica y Traumatología

    Madrid

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

    Madrid

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

    Madrid

  • Hospital U. La Princesa, Servicio de CirugíaOrtopédica y Traumatología

    Madrid

  • Hospital Universitario Ramón y Cajal

    Madrid

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

    Madrid

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

    Majadahonda, Madrid

Other trials in Spain

France5 sites

  • CHU Clermont-Ferrand

    Clermont-Ferrand

  • Department of Orthopaedic Surgery, Hospital Henri Mondor

    Créteil

  • Department of Orthopaedic Surgery, CHU Nantes

    Nantes

  • Department of Orthopaedic Surgery Toulouse University Hospital

    Toulouse

  • Department of Orthopaedic Surgery, CHU Tours

    Tours, 37044

Other trials in France

Germany4 sites

  • Universitätsklinikum Frankfurt, Department of Trauma, Hand and Reconstructive Surgery

    Frankfurt

  • Universitätsklinikum Freiburg, Klinik für Orthopädie und Unfallchirurgie

    Freiburg im Breisgau

  • Universitätsklinikum München

    Munich

  • Department of Orthopaedic Trauma, University of Ulm

    Ulm, 8907581

Other trials in Germany

Italy3 sites

  • Istituto Ortopedico Rizzoli, SSD Fisiopatologia Ortopedica e Medicina Rigenerativa

    Bologna, 40136

  • Arienda Spedali Civili di Brescia II Ortopedia e Traumatologia

    Brescia

  • Istituto Ortopedico Galeazzi, Chirugia dell´Anca l

    Milan

Other trials in Italy

About this study

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

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.

Read the 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.

Being tested
Cultured Mesenchymal Stem Cells, Autologous iliac crest graft
Keywords
Non-union, Advanced therapies, Mesenchymal stem cells, Long bone
Medical subject headings
Fractures, Ununited

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cultured Mesenchymal Stem CellsBiological

    Cultured Mesenchymal Stem Cells obtained from expanded bone marrow

  • Autologous iliac crest graftProcedure or surgery

    Autologous iliac crest grafting

Study groups in NCT03325504
Study groupRoleWhat they receive
hBM-MSCs-Low DoseExperimentalAutologous Cultured Mesenchymal Stem Cells +Biomaterial (Low Dose): 100x106 cells
Receives: Biological: Cultured Mesenchymal Stem Cells
hBM-MSCs-High DoseExperimentalAutologous Cultured Mesenchymal Stem Cells+Biomaterial (High Dose): 200x106 cells
Receives: Biological: Cultured Mesenchymal Stem Cells
Autologous iliac crest graftActive comparatorAutologous Iliac Crest Grafting
Receives: Procedure: Autologous iliac crest graft

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Bone consolidation

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

    Measured: 12 months after treatment

Secondary outcomes (5)

  1. Bone consolidation

    To compare bone consolidation between the experimental arms and the comparator

    Measured: 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.

    Measured: 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.

    Measured: 6, 12 and 24 months

  4. Complications

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

    Measured: 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.

    Measured: 6, 12 and 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2017
  2. Study start5 Sep 2017
  3. Primary completion17 Oct 2022
  4. Study completion15 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
46 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03325504
Sponsor's protocol ID
ORTHOUNION
Other IDs
2015-000431-32, EUCTR2015-000431-32-ES, 2015
Acronym
ORTHOUNION
Status last verified
Dec 2024
First submitted
25 Oct 2017
Last updated
4 Dec 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

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

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cultured Mesenchymal Stem Cells and Autologous iliac crest graft in people with Non Union Fracture, run by Universidad Autonoma de Madrid at 19 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in Spain, France, Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Bone consolidation (time frame: 12 months after treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03325504, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2024.

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