A Prospective Study of the Safety and Efficacy of 3D-printed Non-rigid Biomimetic Implant in Cervical and Thoracolumbar Spine

Official title

A Prospective Study of the Safety and Efficacy of 3D-printed Custom-made Non-rigid Biomimetic Implant for Anterior Column Reconstruction in Cervical and Thoracolumbar Spine

Overview

Vertebral body resection is a wide accepted procedure in tumor resection, deformity correction, and anterior decompression in spondylosis, ossification of posterior longitudinal ligaments, and spondylodiscitis surgery. However, reconstruction of segmental defect is still challenging to spine surgeon, especially in 3-column resection, such as total en bloc spondylectomy in tumor patients. Various graft or prosthesis for reconstruction has been reported, such as structural allograft, Harms mesh cages, expandable cages, and carbon fiber stackable cages. There are no high evidence level study examining the superiority of those different methods. Recently, 3D printed vertebral body replacement has been reported in different disease entities as well, such as tumor, Kümmell's disease in osteoporosis, and spondylosis. 3D printed implant comes with superiority in production of complex geometries and regularity of the fine surface detailed that promote bone ingrowth. Although, 3D-printed titanium vertebra could achieved bone integration in human, a systemic review showed that the subsidence noted in 31.4% of spine surgery with 3D printed implants. In spine surgery, the fixation construct is sufficiently stiff, interbody motion can be reduced, and loading sharing promotes bone fusion. On the other hand, if the reconstruction is too stiff, stress shielding at fusion site occurs. The concept of dynamic fusion, as opposed to rigid fusion, has been demonstrated by an anterior cervical interbody fusion study in porcine model, demonstrating good bone formation, less postfusion stiffness, and a trend to less subsidence. Thus, we developed a 3D printed, custom-made, biomimetic prosthesis, with non-rigid structure, which has been tested in biomechanical study and porcine model, showing good bone formation and less stiffness as well. Therefore, we proposed a prospective clinical study to investigate safety, subsidence, and fusion of this prosthesis.

Detailed description

This is a single-arm prospective observational phase I clinical study to investigate the safety of the non-rigid 3D printed custom-made biomimetic implant. The implants are made of Titanium alloy. Patient receiving 1- to 3-level corpectomy at cervical and thoracolumbar spine. At first stage, we plan to enroll 3 cervical patients, and 3 thoracolumbar patients with non-rigid 3D printed custom-made biomimetic reconstructions. After 3 months observation after the last patients enrolled, we will conduct an interim investigation to investigate those 6 patients. if there is no re-operations due to acute post-operative reconstruction failure. We will continue the study. Total 9 cervical patients, and 9 thoracolumbar patients will be enrolled. Patients are evaluated preoperatively, right after surgery, and 1, 3, 6, 12 months postoperatively. Measure outcomes included overall success, VAS neck and back pain, patient satisfaction, anxiety score, SF-12 MCS/PCS, complications, subsequent surgery rate, and subsidence and fusion rate on radiological examination. Radiological evaluation, including X-ray and computed tomography, will be done pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively. In addition, neck disability index (NDI) will be evaluated in cervical patents, and SORGSQ 2.0 self-reported questionnaire will be applied for all oncology patients. The primary endpoint was a FDA composite definition of success comprising clinical improvement and absence of major complications and secondary surgery events.

Interventions

• Device 3D-printed custom-made non-rigid biomimetic implant
  We developed a 3D printed, custom-made, biomimetic prosthesis, with non-rigid structure, which has been tested in biomechanical study and porcine model, showing good bone formation and less stiffness as well. Therefore, we proposed a prospective clinical study to investigate safety, subsidence, and fusion of this prosthesis.

Primary outcome measures

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [Time frame: Patient were evaluated at 12 months postoperatively.]

Secondary outcome measures (8)

• Degree of change in the subsidence [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]
• The percentage of patients with successful fusion [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]
• Pain score [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]
• Short form-12 mental component score [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]
• Anxiety score [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]
• Neck Disability Index (NDI) [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]
• Patient Satisfaction Questionnaire [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]
• Short form-12 physical component score [Time frame: Patient were evaluated pre-operatively, immediately after the surgery, and 1, 3, 6, 12 months postoperatively.]

Eligibility criteria

Inclusion criteria

• Age 20 - 79 years;
• Patient meet the indication for 1- to 3- level corpectomy, for primary bone tumor at spine, or metastatic tumor at spine.
• Deficit confirmed by CT, MRI, and X-ray;
• Pathology level located from C3 to L5.
• Physically and mentally able and willing to comply with the protocol;
• Signed informed consent;
• NTU Spine Multidisciplinary Board confirmed tumor excision surgery is indicated.
• Life expectancy longer than 6 months (Tokuhashi Scoring System)

Exclusion criteria

• Patient does not meet the indication of corpectomy, which is under the surveillance.
• More than three vertebrae required corpectomy;
• Corpectomy levels above C3 and below L5
• T-score less than -2.5
• Known allergy to device materials - such as titanium
• Any diseases or conditions that would preclude accurate clinical evaluation;
• Daily, high-dose oral and/or inhaled steroid or a history of chronic use of high dose steroids;
• BMI > 35
• Life expectancy less than 6 months - (Tokuhashi Scoring System)
• The subject has received radiation therapy or chemotherapy at the trial site within one year;
• Anterior spine surgery has been received at or near the spine surgery site;
• The subject has systemic infection,or focal vertebral infection or trauma;
• The subject has endocrine disorders or metabolic disorders known to affect bone formation, such as: Paget's disease, renal osteodystrophy, hypothyroidism;
• The subject has neuromuscular diseases, those at risk of instability, implant fixation failure or postoperative care complications, including: spina bifida, cerebral palsy, and multiple sclerosis;
• Osteopenia, osteomyelitis;
• Pregnant women.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Taiwan · 1 center

• National Taiwan University Hospital — Taipei

Publications

• Bridwell KH, Lenke LG, McEnery KW, Baldus C, Blanke K. Anterior fresh frozen structural allografts in the thoracic and lumbar spine. Do they work if combined with posterior fusion and instrumentation in adult patients with kyphosis or anterior column defects? Spine (Phila Pa 1976). 1995 Jun 15;20(12):1410-8. PMID 7676341
• Lewandrowski KU, Hecht AC, DeLaney TF, Chapman PA, Hornicek FJ, Pedlow FX. Anterior spinal arthrodesis with structural cortical allografts and instrumentation for spine tumor surgery. Spine (Phila Pa 1976). 2004 May 15;29(10):1150-8; discussion 1159. doi: 10.1097/00007632-200405150-00019. PMID 15131446
• Dvorak MF, Kwon BK, Fisher CG, Eiserloh HL 3rd, Boyd M, Wing PC. Effectiveness of titanium mesh cylindrical cages in anterior column reconstruction after thoracic and lumbar vertebral body resection. Spine (Phila Pa 1976). 2003 May 1;28(9):902-8. doi: 10.1097/01.BRS.0000058712.88053.13. PMID 12942006
• Viswanathan A, Abd-El-Barr MM, Doppenberg E, Suki D, Gokaslan Z, Mendel E, Rao G, Rhines LD. Initial experience with the use of an expandable titanium cage as a vertebral body replacement in patients with tumors of the spinal column: a report of 95 patients. Eur Spine J. 2012 Jan;21(1):84-92. doi: 10.1007/s00586-011-1882-7. Epub 2011 Jun 18. PMID 21681631
• Boriani S, Biagini R, Bandiera S, Gasbarrini A, De Iure F. Reconstruction of the anterior column of the thoracic and lumbar spine with a carbon fiber stackable cage system. Orthopedics. 2002 Jan;25(1):37-42. doi: 10.3928/0147-7447-20020101-14. PMID 11811240
• Xu N, Wei F, Liu X, Jiang L, Cai H, Li Z, Yu M, Wu F, Liu Z. Reconstruction of the Upper Cervical Spine Using a Personalized 3D-Printed Vertebral Body in an Adolescent With Ewing Sarcoma. Spine (Phila Pa 1976). 2016 Jan;41(1):E50-4. doi: 10.1097/BRS.0000000000001179. PMID 26335676
• Glennie RA, Rampersaud YR, Boriani S, Reynolds JJ, Williams R, Gokaslan ZL, Schmidt MH, Varga PP, Fisher CG. A Systematic Review With Consensus Expert Opinion of Best Reconstructive Techniques After Osseous En Bloc Spinal Column Tumor Resection. Spine (Phila Pa 1976). 2016 Oct 15;41 Suppl 20:S205-S211. doi: 10.1097/BRS.0000000000001835. PMID 27488296
• Choy WJ, Mobbs RJ, Wilcox B, Phan S, Phan K, Sutterlin CE 3rd. Reconstruction of Thoracic Spine Using a Personalized 3D-Printed Vertebral Body in Adolescent with T9 Primary Bone Tumor. World Neurosurg. 2017 Sep;105:1032.e13-1032.e17. doi: 10.1016/j.wneu.2017.05.133. Epub 2017 May 31. PMID 28578109

Identifiers

NCT: NCT05396222 · 202202015DIPC

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗