Efficacy of DBM on Fractures of the Shinbone (Tibia)
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|ClinicalTrials.gov Identifier: NCT00299052|
Recruitment Status : Completed
First Posted : March 6, 2006
Last Update Posted : September 24, 2013
|First Submitted Date ICMJE||March 2, 2006|
|First Posted Date ICMJE||March 6, 2006|
|Last Update Posted Date||September 24, 2013|
|Study Start Date ICMJE||March 2006|
|Actual Primary Completion Date||December 2007 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Fracture healing [ Time Frame: Weeks 0-3, 4-6, 7-8, 12 and 16-24 after surgery ]|
|Original Primary Outcome Measures ICMJE
||Fracture healing at 4 months|
|Change History||Complete list of historical versions of study NCT00299052 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Efficacy of DBM on Fractures of the Shinbone (Tibia)|
|Official Title ICMJE||The Efficacy of Demineralized Bone Matrix and Autogenous Bone Graft in Accelerated Fracture Healing in Closed Tibia Fracture|
The Tibia bone (shinbone) is located in the leg, itis the most frequently fractured bone in the body and has very poor blood supply because it is surrounded by skin and fat instead of muscle like the thighbone causing healing problems. Problems frequently found during the healing process are malunion (bone heals in the wrong place), nonunion (the bone never heals), and compartment syndrome (a big inflammation of muscle that causes compression of nerves and blood vessels) with necrosis (death) of tissue. Surgeons have tried to decrease these problems by using different surgical techniques and substances to accelerate healing. Substances frequently used in fractures are bone grafts. Bone grafts are normally obtained from the wrist or the hip bone, and sometimes can cause other complications varying from pain to infection. To avoid complications, investigators have used alternatives such as obtaining bone from donors. The donor bone grafts are carefully analyzed and cleaned to ensure they will not cause problems for the receiver. Bone obtained from donors is called Demineralized Bone Matrix (DBM). DBM has proved to be very effective in helping fractures to heal faster and we want to use it in patients with tibia fractures.
This study is important because DBM can improve the way tibia fractures are treated and could have the potential to decrease the time patients must stay in the hospital. DBM could improve healing time and diminish overall costs. Also, with the use of DBM plus reamings, patients will have fewer complications like pain and infection.
Duration This study will last for 24 months.
Location Emory Orthopedic Service at Grady Hospital
Background The tibia is the most common fractured bone. 14 It is also the bone with the higher incidence of open wounds because of the tibia proximity with the skin. 14 This bone is often in high risk of malunion, nonunion, infection, and other complications because of the tibia's precarious blood supply, and it is also associated with compartment syndrome in 1 to 9 % of cases. 10,14 Even though relatively new surgical procedures such as intramedullary nailing have increase the function recovery of this patients, still much is to be done to assure the proper evolution of the patients with tibia fractures. 10 It is important to find an adjuvant that will help with this recovery. It has been postulated that the use of bone graft could help in this process but there is more to be analyzed to drawn any definitively conclusion.
Tibia fractures are often part of the injuries in the polytrauma patient. Complicated fractures produced by trauma are often in the need for bone graft. Bone graft is usually obtained from the hip or the distal radius and the procedure is not exempt of complications such as pain, infection and increased hospitalization stay. In order to avoid these events, bone graft substitutes have been developed but most of them are expensive. 11 An example of this is bone morphogenic proteins (BMPs). BMPs have shown a high efficacy rate but cost wise, they could be prohibitive. 11 DBM could be a reasonable alternative and tentatively could have the same efficacy and less antigenic risks 5,9,11. Previous well designed studies have demonstrated the efficacy of demineralized bone matrix in fracture healing of non-unions, total joint osteolytic lesions, benign bone cysts and spine fusions.3-9,11-13 It has even proved it potential efficacy in restoring cartilage surface 7. The importance of this findings support the idea of using DBMs in other applications that could beneficiate the trauma patient.
DBMs are manufactured by different companies and they are available in different presentations. Most important, they vary also in their efficacy. The efficacy of a DBM depends mainly on it osteoconductivity and osteoinductivity 1,5. The differences in osteoconductivity and osteoinductivity between the available DBMs could represent a factor that limits the host's response to the graft 12. According to Louis-Ugbo et al, even the different presentations of DBM's could cause different host responses. 11 This is why it is very important to find a DBM that not only is highly effective, but also has the adequate presentation to be use in trauma fracture patients that require an acute treatment. In a study done by Cammisa et al they asseverate that the value of Grafton® is based upon not only the high osteoconductivity and osteoinductivity that the product presents, but also the fact that the gel formulation allows a mixture with allograft that helps to reach difficult graft sites 3. Other studies have shown that the putty presentation of Grafton® could be even higher in inductive properties 3. A previously done study at Grady Hospital conducted by our service reported an enhanced fracture healing in high energy tibial fractures treated with percutaneous injection of bone marrow with Grafton® acutely (reference to be inserted). Our experience support the hypothesis that Grafton® could be also valuable in the treatment of closed tibia diaphyseal fractures, with a smaller healing frame, decreased hospitalization time and early return to work.
This study would randomize consecutive patients presenting closed tibia fractures into two groups:
We will randomize the patients using a list containing the patient research numbers and research groups. The research number will be assigned in order of presentation.
During the operative procedure, the patient will undergo the surgery as usual. In this particular surgery, the surgeon needs to follow the following steps:
The Grafton® mixture will be prepared by mixing the exceeding bone produced during reaming and the Putty Grafton® form. This preparation will be added during the surgery, before the permanent nail is situated. The mixture will be placed in the canal and positioned in the fracture site with the ball-tipped guide. Fluoroscopy images will be taken to assure the proper localization of the mixture. After this step, the permanent nail will be placed.
Both groups would undergo standard X-rays at appropriate times. Callus formation would be determined by standard radiographic (bridging callus measurement) and clinical evaluation (decreased pain at rest, with standing position and during ambulation)4. There will not be any alteration in length of stay or post-operative regimen. There will be scheduled post-op visits (one month, 6 weeks and 8 weeks) when X-rays of the tibia will be taken (AP, lateral and both oblique).
We will follow patients during their scheduled post-op visitis. They will be scheduled as follows:
Post op visit 1: 1 month after surgery Post op visit 2: 6 weeks after surgery Post op visit 3: 12 weeks after surgery Post op visit 4: 16 weeks after surgery Post op visit 5: 20 weeks after surgery. If necessary, we will include a visit 6 or 7 after 1 year or earlier according to the patient's needs.
Statistical Analysis Statistical analysis will be achieved by using Fisher's exact test 4. A P value <0.05 will be considered as statistically significant 4. For this pilot study we will enroll 30 patients, 15 per group, but we are planning to extend this number to 50 patients in a future, multicenter, randomized study. Using a two-sample t-test, the following analyses have been performed assuming a normal distribution of 2 samples with equal variances. If the mean time to fracture healing in group 1 is 42 days compared to 35 days for group 2, with a common standard deviation of 14 days for both groups, a sample size of 50 patients will be yield a significance level of .5 and power of .80.
Potential Risks Grafton® was associated with acute tubular necrosis in an animal study done with athymic rats 2,9. This study's authors suggested to restrain the use of DBM in children or patients with renal diseases 2,9. These findings have not been corroborated with any other study at the moment and there are some other points to be analyzed such as the associated materials used with Grafton®. In any case, we will not include patients with any type of renal disease or patients under the age of 18 years old in the present study.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date||September 2008|
|Actual Primary Completion Date||December 2007 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00299052|
|Other Study ID Numbers ICMJE||1272-2005
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Thomas Moore, Emory University|
|Study Sponsor ICMJE||Emory University|
|Collaborators ICMJE||Not Provided|
|PRS Account||Emory University|
|Verification Date||September 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP