Pilot Clinical Trial of CPC/rhBMP-2 Microffolds as Bone Substitute for Bone Regeneration

Study Overview
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Brief Summary
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Objective: The investigators initiated a pilot clinical study to test safety and preliminary efficacy in humans (bone tissue repairing capacity) and to evaluate standard clinical and rehabilitation protocols. Summary Background Data: Bone tissue engineering scaffolds loading growth factors have been considered as the most perspective among all bone substitutes, yet little progress of its clinical translation has been made. The concept of micro-scaffolds was proposed in this study to provide a trajectory to its clinical translation. Methods: Pre-cured CPC/rhBMP-2 micro-scaffolds have been successfully developed and further applied as an easy-to-operate filler for bone regeneration in a pilot clinical study. Patients of tibial plateau fractures, proximal humeral fractures, or calcaneal fractures at a similar level of severity were randomly divided into two groups and treated by CPC/rhBMP-2 microffolds or traditional CPC paste (control group).

Detailed Description
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Objective: The investigators initiated a pilot clinical study to test safety and preliminary efficacy in humans (bone tissue repairing capacity) and to evaluate standard clinical and rehabilitation protocols. Summary Background Data: Bone tissue engineering scaffolds loading growth factors have been considered as the most perspective among all bone substitutes, yet little progress of its clinical translation has been made. The concept of micro-scaffolds was proposed in this study to provide a trajectory to its clinical translation. Methods: Pre-cured CPC/rhBMP-2 micro-scaffolds have been successfully developed and further applied as an easy-to-operate filler for bone regeneration in a pilot clinical study. Patients of tibial plateau fractures, proximal humeral fractures, or calcaneal fractures at a similar level of severity were randomly divided into two groups and treated by CPC/rhBMP-2 microffolds or traditional CPC paste (control group).

Official Title
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Pilot Clinical Trial of CPC/rhBMP-2 Microffolds as Bone Substitute for Bone Regeneration

Conditions
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Bone Fracture

Intervention / Treatment
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* Procedure: Minimally invasive internal fixation surgeries
* Device: CPC/rhBMP-2 micro-scaffolds
* Device: CPC paste


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 16 70 years. Tibial plateau fractures, proximal humeral fractures, or calcaneal fractures at a similar level of severity. An understanding of the rehabilitation protocol and willing to follow it. An agreement to postoperative visits and tests. Signed an informed subject consent form. Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 70 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CPC/rhBMP-2<br>All operations were done by doctors titled with associate chief physician or above. Procedures were performed under general anesthesia in a tertiary care medical center. A minimally invasive internal fixation method had been applied in the surgeries. In brief, the patients with fracture were treated by reduction of fracture first of all, the correction of displacement, and the angle of the deformity, and the use of metal implants were fixed, and the collapse of the cancellous bone was filled with CPC/rhBMP-2 microffolds (product of Shanghai Rebone Biomaterials Co., Ltd, following the manufacturer's instruction), which was compacted and prevented from filling material into the joint cavity. | Procedure: Minimally invasive internal fixation surgeries<br> <br> Device: CPC/rhBMP-2 micro-scaffolds<br> <br> |
| Active Comparator: CPC<br>All operations were done by doctors titled with associate chief physician or above. Procedures were performed under general anesthesia in a tertiary care medical center. A minimally invasive internal fixation method had been applied in the surgeries. In brief, the patients with fracture were treated by reduction of fracture first of all, the correction of displacement, and the angle of the deformity, and the use of metal implants were fixed, and the collapse of the cancellous bone was filled with CPC paste (product of Shanghai Rebone Biomaterials Co., Ltd, following the manufacturer's instruction), which was compacted and prevented from filling material into the joint cavity. | Procedure: Minimally invasive internal fixation surgeries<br> <br> Device: CPC paste<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| X-ray | X-ray radiography at different time intervals after implantation was employed to observe the osseointegration of the implanted microffolds to host bone and the degradation of the material. | Pre-operation; 1, 2, 3, 4, 6, 8, 12, 18 and 24 months post-operation. | 
| Clinical examination | The assessment was based on clinical examination. After the CPC implantation, all patients were observed according to the following indexes: allergic or toxic reactions, rash or high fever. | 1 week post-operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Function scoring - IOWA knee score | The functional recovery was recorded at each follow-up time point using IOWA knee score in cases of tibial plateau fractures. The IOWA knee score is a questionnaire and clinical-examination-based evaluation of the function of the knee. The knee score is a five- category measurement, which includes activities of daily living, freedom from pain, gait, aid dependence, deformity and range of movement. The scores are grouped into excellent (90 to 100), good (80 to 89), fair (70 to 79) and poor (under 70) categories. | 1, 2, 3, 4, 6, 8 and 12 months post-operation. | 
| Function scoring - IOWA ankle score | The functional recovery was recorded at each follow-up time point using IOWA ankle score in cases of calcaneal fractures. The IOWA ankle score is a questionnaire and clinical-examination-based evaluation of the function of the ankle. The ankle score is a four-category measurement of function, freedom from pain, gait and range of movement. The scores are grouped into excellent (90 to 100), good (80 to 89), fair (70 to 79) and poor (under 70) categories. | 1, 2, 3, 4, 6, 8 and 12 months post-operation. | 
| Function scoring - NEER shoulder score | The functional recovery was recorded at each follow-up time point using Neer shoulder score in cases of proximal humeral fractures. Neer shoulder score has three parts: scoring of pain during the previous week by patients (verbal rating scale); clinical testing of function (muscle strength, reaching ability, and stability) and active range of motion; and an anatomical or radiological evaluation. The scores are grouped into excellent (90 to 100), good (80 to 89), fair (70 to 79) and poor (under 70) categories. | 1, 2, 3, 4, 6, 8 and 12 months post-operation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bone substitute, CPC, rhBMP-2