Evaluation of Cranioplasty Using Native Bone Autograft Versus Synthetic Bone Allograft

Study Overview
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Brief Summary
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Elevated intracranial pressure (ICP) is a common neurosurgical emergency that may arise from several conditions, which cause an intracranial mass effect. In the case of conservatively refractory ICP elevation, one viable treatment option is ICP-lowering surgery, i.e., decompressive craniectomy (DC) in which a large portion of the skull bone is removed and the dura mater opened, creating more room for the brain tissue to expand and thus reducing the ICP. A successful CP will restore the contour of the cranium, protect the brain, and ensure a natural ICP, and some patients also show neurological improvement post-CP. Thus, CP has a great potential for improving the patient's quality of life. Bone flap resorption (BFR) implies weakening and loosening of the autologous bone flap after reimplantation and is regarded as a late CP complication involving nonunion of the bone flap with the surrounding bone margins and cavity formation in the flap itself, which eventually necessitates removal of the bone flap and a new CP using a synthetic implant. These additional operations increase costs and necessitate further hospital stays, while rendering the patient vulnerable to additional complications. Prior research performed as part of the FDA approval process has shown the ASPCI's to be a safe and effective means of performing cranial reconstruction, the anticipated risks do not differ from the risks faced by a patient undergoing either option as they are both currently considered standards of care. This study will evaluate the overall patient outcomes of cranial reconstruction surgery using native bone autograft as compared to using synthetic bone allograft.

Detailed Description
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Elevated intracranial pressure (ICP) is a common neurosurgical emergency that may arise from several conditions, which cause an intracranial mass effect. In the case of conservatively refractory ICP elevation, one viable treatment option is ICP-lowering surgery, i.e., decompressive craniectomy (DC) in which a large portion of the skull bone is removed and the dura mater opened, creating more room for the brain tissue to expand and thus reducing the ICP. In many centers, the bone flap removed in DC is customarily kept deep frozen at -70°C until reimplantation during cranioplasty (CP). The cranium is repaired during CP by returning the previously removed autologous bone flap or by placing an artificial implant in the defect area. A successful CP will restore the contour of the cranium, protect the brain, and ensure a natural ICP, and some patients also show neurological improvement post-CP1-4. Thus, CP has a great potential for improving the patient's quality of life. Although widely regarded as a routine operation, CP often involves serious complications, such as postoperative hemorrhages, surgical site infection (SSI), and, most importantly, resorption of the autologous bone flap5-8. Bone flap resorption (BFR) implies weakening and loosening of the autologous bone flap after reimplantation and is regarded as a late CP complication involving nonunion of the bone flap with the surrounding bone margins and cavity formation in the flap itself, which eventually necessitates removal of the bone flap and a new CP using a synthetic implant. These additional operations increase costs and necessitate further hospital stays, while rendering the patient vulnerable to additional complications. The reported prevalence of BFR with autologous CPs has varied significantly, from 1.4% to 32.0%, with infection rates ranging from 4.6% to 16.4%9-12. CP is a common procedure for cranial reconstruction in the setting of trauma, stroke, skull neoplasm, osteomyelitis, or after procedures that are approached via craniectomy such as microvascular decompression or acoustic neuroma. Recently there have been two major areas of interest presenting in the literature. First, there have been at least 6 manuscripts published on retrospective data comparing autologous bone versus synthetic prosthetic for CP13-18. Each has shown benefit for synthetic prosthetics. However, the community is resistant to implement a treatment pattern where synthetic bone is a first line choice for CP. Therefore, a prospective randomized controlled trial is needed to understand with high confidence the option that is most beneficial for patients. Prior research performed as part of the FDA approval process has shown the ASPCI's to be a safe and effective means of performing cranial reconstruction, the anticipated risks do not differ from the risks faced by a patient undergoing either option as they are both currently considered standards of care. This study will evaluate the overall patient outcomes of cranial reconstruction surgery using native bone autograft as compared to using synthetic bone allograft.

Official Title
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Evaluation of Cranioplasty Using Native Bone Autograft Versus Synthetic Bone Allograft

Conditions
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Surgical Procedure, Unspecified

Intervention / Treatment
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* Device: Synthetic Bone Allograft (ClearFit)
* Other: Autograft


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult patients being considered for CP surgery by the investigating physician at the Life Bridge Health-Sinai Hospital of Baltimore Able to read and speak English, or have LAR who reads and speaks English Patients who need cranial reconstruction Exclusion Criteria: Patients affected by comminuted skull fractures, Patients affected by osteomyelitis, Patients with skull neoplasm and therefore not be candidates for autologous CP Patients who would need to be allocated to one group over the other due to clinical presentation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Interventional Model Description: Participants are assigned to one of two treatment groups.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Autograft group<br>The autologous group will receive bone harvested from the patient's own body | Other: Autograft<br>* Patients in this arm will use patient's own bone<br>|
| Active Comparator: Allograft group (ClearFit)<br>The allograft group will receive a synthetic bone known as ClearFit | Device: Synthetic Bone Allograft (ClearFit)<br>* Patients in this arm will receive ClearFit (synthetic bone allograft)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the surgical and post-operative outcomes (complications) of two standard of care cohorts: autograft versus allograft (ClearFit) | Asses for infection, hematomas, fractures, mobilization and scar retraction, wound site infection, UTI, pneumonia, delayed internal bleeding, reoperation, and hardware failure | intraoperatively | 
| To compare the surgical and post-operative outcomes (complications) of two standard of care cohorts: autograft versus allograft (ClearFit) | Asses for infection, hematomas, fractures, mobilization and scar retraction, wound site infection, UTI, pneumonia, delayed internal bleeding, reoperation, and hardware failure | post-operatively through study completion, an average of 1 year | 
| To compare the surgical and post-operative outcomes (complications) of two standard of care cohorts: autograft versus allograft (ClearFit) | Asses for infection, hematomas, fractures, mobilization and scar retraction, wound site infection, UTI, pneumonia, delayed internal bleeding, reoperation, and hardware failure | 2 weeks post-operation | 
| To compare the surgical and post-operative outcomes (complications) of two standard of care cohorts: autograft versus allograft (ClearFit) | Asses for infection, hematomas, fractures, mobilization and scar retraction, wound site infection, UTI, pneumonia, delayed internal bleeding, reoperation, and hardware failure | 6 weeks post-operation | 
| To compare the surgical and post-operative outcomes (complications) of two standard of care cohorts: autograft versus allograft (ClearFit) | Asses for infection, hematomas, fractures, mobilization and scar retraction, wound site infection, UTI, pneumonia, delayed internal bleeding, reoperation, and hardware failure | 3 months post-operation | 
| To compare the surgical and post-operative outcomes (complications) of two standard of care cohorts: autograft versus allograft (ClearFit) | Asses for infection, hematomas, fractures, mobilization and scar retraction, wound site infection, UTI, pneumonia, delayed internal bleeding, reoperation, and hardware failure | 6 months post-operation | 
| To compare the surgical and post-operative outcomes (complications) of two standard of care cohorts: autograft versus allograft (ClearFit) | Asses for infection, hematomas, fractures, mobilization and scar retraction, wound site infection, UTI, pneumonia, delayed internal bleeding, reoperation, and hardware failure | 1 year post-operation | 
| To assess change in surgical and post-operative outcomes (function) of two standard of care cohorts: autograft versus allograft (ClearFit) | Barthel index consisting of 10 questions - score range 0 (completely dependent)- 20 (completely independent) | 24 hours post operation, 2 weeks, 6 weeks, 3 months, 6 months, 1-year | 
| To assess change in surgical and post-operative outcomes (function) of two standard of care cohorts: autograft versus allograft (ClearFit) | Karnofsky scale (0-100); 0 indicating death and 100 indicating no additional help is needed | 24 hours post operation, 2 weeks, 6 weeks, 3 months, 6 months, 1-year | 
| To assess change the surgical and post-operative outcomes (function) of two standard of care cohorts: autograft versus allograft (ClearFit) | Glasgow Outcome Scale (GOS) on a scale of 1(death)- 5 (good recovery) | 24 hours post operation, 2 weeks, 6 weeks, 3 months, 6 months, 1-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess change in pain using the Visual Analogue Scale (VAS) Pain scale | Assess change in pain; ranking pain on a scale of 1 (least amount of pain)-10 (greatest amount of pain) | 24 hours post operation, 2 weeks, 6 weeks, 3 months, 6 months, and 1 year | 
| To assess change in disability using the Oswestry Disability Index (ODI) | Assess change in disability; 6 item questionnaire; scores range from 0(minimal d disability)-60 (bed bound) | 2 weeks, 6 weeks, 3 months, 6 months, and 1 year | 
| To assess change in quality of life using the Health and Quality of life improvement (SF-36) | Assess change in quality of life; 36-item questionnaire, 0 (favorable health state life)-100 (poor health state) | 2 weeks, 6 weeks, 3 months, 6 months, and 1 year | 
| To assess overall patient satisfaction of two standard of care cohorts: autograft versus allograft (ClearFit)Patient Satisfaction | Patient Satisfaction questionnaire; 5 questions; scores range from 0(unsatisfied) - 22(completely satisfied) | at the 2 week visit |