BST-CarGel® Treatment Maintains Cartilage Repair Superiority over Microfracture at 5 Years in a Multicenter Randomized Controlled Trial

Matthew S Shive, William D Stanish, Robert McCormack, Francisco Forriol, Nicholas Mohtadi, Stéphane Pelet, Jacques Desnoyers, Stéphane Méthot, Kendra Vehik, Alberto Restrepo, Matthew S Shive, William D Stanish, Robert McCormack, Francisco Forriol, Nicholas Mohtadi, Stéphane Pelet, Jacques Desnoyers, Stéphane Méthot, Kendra Vehik, Alberto Restrepo

Abstract

Objective: The efficacy and safety of BST-CarGel®, a chitosan scaffold for cartilage repair was compared with microfracture alone at 1 year during a multicenter randomized controlled trial in the knee. This report was undertaken to investigate 5-year structural and clinical outcomes.

Design: The international randomized controlled trial enrolled 80 patients, aged 18 to 55 years, with grade III or IV focal lesions on the femoral condyles. Patients were randomized to receive BST-CarGel® treatment or microfracture alone, and followed standardized 12-week rehabilitation. Co-primary endpoints of repair tissue quantity and quality were evaluated by 3-dimensional MRI quantification of the degree of lesion filling (%) and T2 relaxation times. Secondary endpoints were clinical benefit measured with WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) questionnaires and safety. General estimating equations were used for longitudinal statistical analysis of repeated measures.

Results: Blinded MRI analysis demonstrated that BST-CarGel®-treated patients showed a significantly greater treatment effect for lesion filling (P = 0.017) over 5 years compared with microfracture alone. A significantly greater treatment effect for BST-CarGel® was also found for repair tissue T2 relaxation times (P = 0.026), which were closer to native cartilage compared to the microfracture group. BST-CarGel® and microfracture groups showed highly significant improvement at 5 years from pretreatment baseline for each WOMAC subscale (P < 0.0001), and there were no differences between the treatment groups. Safety was comparable for both groups.

Conclusions: BST-CarGel® was shown to be an effective mid-term cartilage repair treatment. At 5 years, BST-CarGel® treatment resulted in sustained and significantly superior repair tissue quantity and quality over microfracture alone. Clinical benefit following BST-CarGel® and microfracture treatment were highly significant over baseline levels.

Keywords: cartilage repair; chitosan; microfracture; quantitative MRI; scaffold.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: One or more of the authors received payments, either directly or indirectly (i.e. via their institution), from a third party in support of an aspect of this work.

Figures

Figure 1.
Figure 1.
Longitudinal analysis of repeated measures using general estimating equations (GEE) for the quantity and quality of repair cartilage over 5 years posttreatment. Values represent least squares means adjusted for lesion volume and the standard error. (A) Lesion %Fill: Statistically significant improvement for the BST-CarGel® group over microfacture (MFX) (P = 0.017). Lesion %Fill is calculated from the ratio of new repair tissue volume to the baseline (postdebridement) cartilage lesion volume at 1-month posttreatment. (B) Repair tissue T2 relaxation times: Statistically significant improvement for the BST-CarGel® group over MFX (P = 0.026). Mean T2 is derived from the entire repair cartilage volume. Dashed line represents mean ipsilateral native cartilage T2 value.
Figure 2.
Figure 2.
Improvement in clinical outcomes following (A) BST-CarGel® and (B) microfracture (MFX) treatments assessed by Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) (visual analogue scale) scores. Change from baseline was statistically significant for all subscales (P < 0.0001) at 1 and 5 years for BST-CarGel® and MFX groups. Values represent means and standard errors. Lower numbers represent better outcomes.
Figure 3.
Figure 3.
Longitudinal analysis of repeated measures using general estimating equations (GEE) for Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) scoring over 5 years posttreatment. Values represent mean change from baseline adjusted for baseline and standard errors. Similar improvements for both BST-CarGel® and microfracture (MFX) groups were observed for subscales (A) Pain (P = 0.474), (B) Stiffness (P = 0.236), and (C) Function (P = 0.326).

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