Multiregion BHA in Open Tibia Fractures

Study Overview
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Brief Summary
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This clinical study is being conducted to demonstrate the safety and effectiveness of the Bone Healing Accelerant (BHA) product when applied to tibia (leg bone) fractures with an external wound or skin break (also called open tibia fractures). It is hypothesized that by 6 months, the number of subjects with successful bone healing will be greater in the BHA-treated group compared to subjects treated with standard of care alone. Open tibia fractures were chosen for this study because healing rates are typically longer than for other bone fractures due to the limited vascular supply, limited soft tissue coverage, and higher risk of infection.

Official Title
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A Multiregion, Randomized, Controlled, Blinded Study of the Safety and Efficacy of Bone Healing Accelerant Versus Standard of Care in Subjects With Open Tibia Fractures

Conditions
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Tibial Fractures

Intervention / Treatment
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* Combination Product: BHA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is between the ages of 18-75 inclusive at time of randomization. Patient has an acute open Gustilo-Anderson Type IIIA or IIIB fracture of the tibia shaft, with or without a fibula fracture, secondary to trauma. Patient received antibiotic treatment within 2 hours of presentation at initial medical facility. Patient underwent their first operative debridement within 24 hours of presentation at initial medical facility. Patient is scheduled to have DWC within 14 days of initial injury. The tibia fracture requires open fracture reduction and internal fixation with intramedullary (IM) nailing; - IM nailing has been cross-locked for stability with a 4-5mm interlock, with a minimum of 1 static screw above the fracture site and 1 static screw below the fracture site, and All IM nails have a diameter between 8.5-12mm with 1.0-1.5mm over-reaming of the canal. The temporary use of external fixation prior to IM rodding and DWC is allowed. Upon stabilization of the tibia fracture, the patient has a cortical deficit of less than or equal to 1.0cm involving no more than 50% of the tibia circumference. The cortical deficit of the residual 50% circumference must be less than 1.0cm. Gap assessments to be made with calibrated radiographs or visual inspection. In addition, patients are not likely to require a secondary procedure(s) to promote bone healing. BHA is able to be applied through existing soft tissue defects created by the injury or those created during surgical treatment. No new incisions should be required specifically for application of BHA. Patient is willing and able to comply with all study procedures including all pre-operative, post-operative and rehabilitation requirements. Patient is able to give voluntary IC to participate and has signed an IC form specific to this study prior to study treatment and DWC. Patients of childbearing potential must use adequate methods of contraception during the duration of follow-up (12-months). Adequate methods include abstinence, female and male sterilization, hormonal contraceptives, intrauterine devices (IUDs), implants, injectables, and double barrier methods. Exclusion Criteria: Patients who are currently participating in another investigational trial or having participated in a clinical investigation within the last 90 days or intend to during the course of the study. Patients who are currently prisoners. Patients who are unable to give informed consent. Patients who are skeletally immature (<18 years of age or radiographic evidence of open tibial physes). Patients with Type I, II, or IIIC open tibia fractures according to the Gustilo-Anderson classification. Current injury is a pathological fracture. Patients with additional injuries that could impact their ability to complete the required assessments and postoperative rehabilitation. Patients with immune deficiency or history of auto-immune disease. Patients with an active malignancy or a history of any invasive malignancy (except non-melanoma skin cancer), unless the patient has been treated with curative intent and there have been no clinical signs or symptoms of malignancy for at least 5 years. Patients with any medical condition or life circumstances that in the surgeon's opinion could impact their ability to return for follow-up visits and/or complete the required assessments and postoperative rehabilitation. Patients who are known to have anaphylactic or severe systemic reaction to human blood products, genipin, β-TCP, glycerin or to other components of the investigative product formulation. Female patients of child-bearing potential who meet any of the following criteria: Patient is currently pregnant (prior diagnosis or a positive pregnancy test at baseline), or planning to become pregnant any time during the course of the study Currently breastfeeding or planning to breastfeed at any time during the course of the study Upon stabilization of the tibia fracture, the patient has a bone gap greater than 1.0cm apparent by calibrated radiographs or by visual inspection and/or the patient is highly likely to require secondary intervention procedure(s), surgical or nonsurgical (e.g., bone stimulation or ultrasound treatment) for the index fracture. Patients who have mal-alignment post-IM nailing of >10° in the coronal plane or >15° in the sagittal plane. Patients who received only plates and screws for tibia fracture stabilization. At the time of the DWC surgery, patients who have a planned secondary intervention procedure, surgical or nonsurgical (e.g., bone stimulation or ultrasound treatment) for the index fracture. Patients being treated with any form of local antibiotics at the time of DWC.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BHA<br>Subjects treated with BHA + standard of care | Combination Product: BHA<br>* BHA active ingredients include beta-tricalcium phosphate and a blood-derived component. It is applied directly to the bone fracture and nearby viable bone at the time of wound closure.<br>|
| No Intervention: Control<br>Subjects treated as per standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite healing measure | Proportion of subjects in each arm meeting the healing success criteria. A binary (Yes/No) outcome for overall healing will be derived from the following three outcomes: Radiographic healing as measured by a score of at least 13 on the modified Radiographic Union Scale in Tibia fractures (mRUST, range bad to good 1-16), ambulation as measured by a score of at least 2 on the Function IndeX for Trauma scale (range bad to good 0-3), and no secondary intervention to promote bone healing. All three components must be met for a yes on composite healing. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic healing | Population mean Modified Radiographic Union Scale in Tibia Fractures (mRUST) scores (range bad to good is 4-16) | 6 months | 
| Secondary intervention (surgical or nonsurgical) | Proportion of subjects not having secondary intervention conducted specifically to promote bone healing needed | 6 months | 
| Surgical Site Infection | Proportion of subjects having surgical site infection through 12 months as determined by CDC guidelines | 12 months |