Clinical trial NCT00512434: Percutaneous Autologous Bone-marrow Grafting for Open Tibial Shaft Fracture
Official title: Injection of Concentrated Autologous Bone-marrow (IMOCA) and Bone Union of Open Tibial Shaft Fracture: Randomized Study to Assess Efficiency of IMOCA in Addition to Standard of Care.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Tibial Fractures
Fractures, Open
Keywords: tibial
shaft
fracture
open
bone-marrow
graft
injection
mesenchymal stem cell
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
First posted: 2007-08-07
Enrollment: 85
Sex: ALL
Minimum age (years): 17
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The treatment of open tibial shaft fracture is often complicated by delayed union or non-union. The objective of this study is to evaluate the efficacy of autologous concentrated bone-marrow to accelerate healing of open tibial shaft fractures and to reduce the need for secondary intervention.

In a prospective, randomized, controlled, single-blind study, 186 patients with an open tibial will be randomized to receive either the standard of care (fixation by nail or external fixator and routine soft-tissue management), or the standard of care with percutaneous injection, one month after fracture, of autologous concentrated bone-marrow. Randomization will be stratified by severity of the open wound. The primary outcome measure will be the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months post-fracture.

Detailed description: This study will be conducted at 13 University Hospitals in France. The protocol has been approved by the institutional review board. After written informed consent, patients will be randomized, in the days after the fracture in 2 groups of 93 patients : 1) the control group (standard of care only: fixation by nail or external fixator and routine soft-tissue management) and 2) the study group (standard of care with percutaneous injection, one month after fracture, of autologous concentrated bone-marrow). Randomization will be stratified by severity of the open wound and by center. For the wound, strata A comprise Gustilo-Anderson types I, II and III-A and strata B, type III-B.

For the study group, the injection is scheduled at 1 month ± 5 days after the fracture. The techniques have been described by Hernigou (J Bone Joint Surg Am, 2006; 88(sup 1 part 2): 322-327). There are 3 steps: marrow aspiration (300 - 500 g) from iliac crest under general anesthesia, centrifugation in cell therapy unit to obtain a concentrated buffy coat of about 50 ml containing progenitor cells and other mononuclear cells, percutaneous injection in the fracture site of 20-30 ml of the buffy coat under fluoroscopy control.

Apart from the injection, the standard of care is the same for the 2 groups. Patients will be followed for 12 months, with assessments at 1, 2, 3, 6, 9 and 12 months.

All analysis will be based on the intent to treat the population. The primary outcome measure will be the proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve months post fracture. An independent panel of surgeons will evaluate all secondary procedure with the potential of promoting fracture-healing.

An independent evaluation of fracture union will be conducted by a radiology panel blinded to treatment allocation and all other patient data.

An outcome will be considered to be successful when the fracture heal, according to the investigator, without secondary intervention and is radiographically united during patient follow-up.

Eligibility criteria: Inclusion Criteria:

* Age 17 years or more
* Open tibial shaft fracture with Gustilo-Anderson type I, II, III A or B
* Written informed consent
* Affiliated to French Social Security

Exclusion Criteria:

* Circumferential bone loss
* Vascular or nerve injury
* Injury, other than tibial fracture, interfering with weight bearing
* Infection (skin, soft-tissue or bone)
* Disease or treatment interfering with bone union: head injury with coma, pathologic fracture
* Medical history on iliac wing contraindicating bone-marrow aspiration
* Corticoid or immunosuppressive therapy more than one week
* Pregnancy at the day of inclusion in study
* History of positive serology for HIV1+2, HBs, HCV
* Adult in the care of a guardian
* Impossibility to meet at the appointments for the follow-up

Primary outcomes:
measure: Proportion of patients requiring secondary intervention because of delayed union or nonunion within twelve month post fracture.
timeFrame: one year
Secondary outcomes:
measure: Relation between the number of the progenitor available injected with concentrated bone marrow aspirated and the rate of bone union.
timeFrame: one year
measure: Comparison of the rate of complications between the 2 groups.
timeFrame: one year
measure: Economic impact study.
timeFrame: one year
Other outcomes:
Locations:
city: Angers
country: France
facility: UH Angers
city: Besancon
country: France
facility: UH Besançon Jean Minjoz
city: Brest
country: France
facility: UH Brest Cavale Blanche
city: Clermont Ferrand
country: France
facility: UH Clermont Ferrand Gabriel Montpied
city: Grenoble
country: France
facility: UH Grenoble Michallon Hospital
city: Grenoble
country: France
facility: UH Grenoble South Hospital
city: Nancy
country: France
facility: UH Nancy Central Hospital
city: Nantes
country: France
facility: UH Nantes Hôtel Dieu
city: Paris
country: France
facility: UH Pitié Salpétrière AH HP
city: Tours
country: France
facility: UH Tours CHRU Trousseau
city: Tours
country: France
facility: UHTOURS
Study officials:
affiliation: Service d'orthopédie II - CHRU de Tours
name: Philippe Rosset, Pr
role: PRINCIPAL_INVESTIGATOR
References: