Spine Growth Modulation in Early Adolescent Idiopathic Scoliosis: Two-Year Results of Prospective US FDA IDE Pilot Clinical Safety Study of Titanium Clip-Screw Implant

Abstract

Study design: Prospective pilot clinical safety study of novel treatment, consecutive case series from first human use in patients with early adolescent idiopathic scoliosis (AIS).

Objective: The primary purpose was to determine the initial safety of a titanium clip-screw implant system for spine growth modulation. The secondary aim was to document curvatures to 2 years postoperatively.

Summary of background data: Spinal growth modulation was documented in preclinical studies. A prospective pilot clinical safety study was then performed under a Food and Drug Administration (FDA) Investigational Device Exemption (IDE) (www.clinicaltrials.gov Identifier: NCT01465295).

Methods: Six subjects with early AIS underwent thoracoscopic placement of titanium clip-screw devices. Eligibility criteria included only patients at high risk for progression to 50°: single major thoracic curve 25°-40°, age ≥10 years, skeletally immature (Risser 0 plus open triradiate cartilages), and if female, premenarchal. Adverse events (AEs), clinical outcomes, and radiographic measures were documented using Good Clinical Practices.

Results: Six consecutive subjects were enrolled, three females and three males aged 12.1 years (±1.7). AEs included one that was device related-mild device migration at 18 months in the most rapidly progressive curve. Procedure-related AEs were mostly pulmonary. A chylous effusion that met the clinical protocol definition of a serious AE resolved after minimally invasive interventions. Major thoracic curves were 34° (±3°) preoperatively and 38° (±18°) at two years (intrasubject change, 4° ± 18°). At 24 months, curves in 3 patients were >45° and 3 were <40°.

Conclusions: A spine growth modulation system undergoing study under an FDA IDE was determined to be safe. Variability in curve response to the implant was high, ranging from progression to correction. Investigational approval was granted by the US FDA for the next cohort of 30 subjects.

Keywords: Adolescent idiopathic scoliosis; Fusionless; Safety; Spine growth modulation; Titanium.

Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1.

Titanium clip-screw implant construct (size 12 mm) is shown with preloaded screws in four views.

Fig. 2.

Intraoperative fluoroscopic images from the clinical study showing titanium clip with preloaded screws in insertion tool before (left) and after implantation (right). Disc wedging at implantation is shown, with disc height slightly decreased on the implant side and increased on the opposite side. [Reprinted from Reference , Figure 2: Wall EJ, Bylski-Austrow DI, Reynolds JE, et al. Chapter 45. Growth modulation techniques: titanium clip-screw implant system (HemiBridge). In: The growing spine. Management of spinal disorders in young children, 2nd ed, Part VI. Berlin: Springer; 2016:769—81]

Fig. 3.

Major thoracic curvatures by postoperative (PO) time are shown. Mean and standard deviation (gray), and curvatures for each subject (black) are presented. Variability was high, however, the major curvature at 2 years postoperative remained below surgical fusion (PSF) indications (45° - 50°) in a cohort chosen specifically to have a high probability of progression. Mean intrasubject curvature increase from immediately preoperation to 24 months was less than 5°.

Fig. 4.

Lumbar curvatures by postoperative time are shown. Mean and standard deviation (gray), and curvatures for each subject (black) are presented. Mean intrasubject curvature increase from immediately preoperation was less than 5°.

Fig. 5.

Thoracic kyphosis curvatures by postoperative time are shown. Mean and standard deviation (gray), and curvatures for each subject (black) are presented. Mean intrasubject curvature increase from immediately preoperation was less than 5°.

Fig. 6

Radiographic time sequence of most rapidly progressing curvature. Top: Coronal plane (posteroanterior, PA). a) Immediately preoperative, with calibration ring, major thoracic curve, 35°; b) 3 months postoperation, 40.5°; c) 12 months, 49°; d) 22 months, after PSF without clip removal. Bottom: Sagittal plane. e) Immediate preoperative; f) 3 months postoperation; g) 12 months; h) 22 months postoperation. Thoracic hypokyphosis and rib hump are evident throughout the time sequence.

Fig. 7.

Radiographic time sequence of most successful subject results to date. Top: Coronal plane (posteroanterior, PA). a) Immediately preoperative, with calibration ring, major thoracic curve 36°; b) First postoperative standing radiograph, 20°; c) 1 year, 10°; d) 2 years, 12°. This time course showed that the method corrected a thoracic curvature, and altered the progression of a lumbar compensatory curvature, providing evidence of growth modulation in humans by this method. Bottom: Sagittal plane. e) Immediately preoperative; f) First postoperative standing; g) 1 year; h) 2 years. Note improvement in the symmetry of the posterior aspect of the ribs with reduction of rib hump. [Figs 6a—d reprinted from Figure 9, Chapter 45 in Wall EJ, Bylski-Austrow DI, Reynolds JE, et al. Chapter 45. Growth modulation techniques: titanium clip-screw implant system (HemiBridge). In: The growing spine. Management of spinal disorders in young children, 2nd ed, Part VI. Berlin: Springer; 2016:769–81]

Fig. 8.

Radiographs (PA) of major thoracic curvatures from two subjects, one whose curvature progressed (top) and one whose curvature corrected (bottom). Top: Progression. a) Three-month postoperatively radiograph showing implant placement with 29° curve. b) At 18 months postoperatively, two pairs of adjacent implants clearly moved apart from each other, with apparent bone growth between the implants (circled areas) and increase in curvature. Bottom: Correction. a) Radiograph showing immediately preoperative curvature of 36°. b) Six-month postoperative radiograph showing implant placement and curvature reduction to 25°. c) At 2 years postoperatively, curvature was corrected to 12°. In this case, implants remained tightly grouped.