Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2022 Jan-Mar;13(1):19476035221085146.
doi: 10.1177/19476035221085146.

Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial

P Niemeyer  1 , M Hanus  2 , J Belickas  3 , T László  4 , R Gudas  5 , M Fiodorovas  6 , A Cebatorius  6 , M Pastucha  7 , P Hoza  8 , K Magos  9 , K Izadpanah  10 , L Paša  11 , G Vásárhelyi  12 , K Sisák  13 , M Mohyla  14 , C Farkas  15 , O Kessler  16 , S Kybal  17 , R Spiro  18 , A Köhler  19 , A Kirner  19 , S Trattnig  20 , C Gaissmaier  19
Affiliations
Clinical Trial

Treatment of Large Cartilage Defects in the Knee by Hydrogel-Based Autologous Chondrocyte Implantation: Two-Year Results of a Prospective, Multicenter, Single-Arm Phase III Trial

P Niemeyer et al. Cartilage. 2022 Jan-Mar.

Abstract

Objective: To evaluate the clinical outcome of a hydrogel-based autologous chondrocyte implantation (ACI) for large articular cartilage defects in the knee joint.

Design: Prospective, multicenter, single-arm, phase III clinical trial. ACI was performed in 100 patients with focal full-thickness cartilage defects ranging from 4 to 12 cm2 in size. The primary outcome measure was the responder rate at 2 years using the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results: Two years after ACI treatment, 93% of patients were KOOS responders having improved by ≥10 points compared with their pre-operative level. The primary endpoint of the study was met and demonstrated that the KOOS response rate is markedly greater than 40% with a lower 95% CI (confidence interval) of 86.1, more than twice the pre-specified no-effect level. KOOS improvement (least squares mean) was 42.0 ± 1.8 points (95% CI between 38.4 and 45.7). Mean changes from baseline were significant in the overall KOOS and in all 5 KOOS subscores from Month 3 (first measurement) to Month 24 (inclusive) (P < 0.0001). The mean MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score after 24 months reached 80.0 points (95% CI: 70.0-90.0 points) and 92.1 points in lesions ≤ 5 cm2.

Conclusions: Overall, hydrogel-based ACI proved to be a valuable treatment option for patients with large cartilage defects in the knee as demonstrated by early, statistically significant, and clinically meaningful improvement up to 2 years follow-up. Parallel to the clinical improvements, MRI analyses suggested increasing maturation, re-organization, and integration of the repair tissue.

Trial registration: NCT03319797; EudraCT No.: 2016-002817-22.

Keywords: autologous chondrocyte implantation; cartilage repair; hydrogel; knee; large defects.

PubMed Disclaimer

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: S.T. received payment for central MRI assessment by TETEC AG. C.G., A.Kö., and A.Ki. are employees of TETEC AG. R.S. is an employee of Aesculap Biologics LLC. All other authors received an investigator fee as outlined in the initial clinical trial authorization documents and accepted by the corresponding ethics committees.

Figures

Figure 1.
Figure 1.
KOOS responder rates over time through Month 24. Vertical error bars indicate the exact 95% confidence intervals according to Clopper and Pearson. P values are derived from the 1-sided exact binomial test of hypotheses H0: Rate ≤ 40% versus H1: Rate >40%. KOOS = Knee Injury and Osteoarthritis Outcome Score.
Figure 2.
Figure 2.
Scatter plot with linear regression model for overall KOOS change from baseline at Month 24 by prior failed cartilage repair. KOOS = Knee Injury and Osteoarthritis Outcome Score.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Heir S, Nerhus TK, Rotterud JH, Løken S, Ekeland A, Engebretsen L, et al.. Focal cartilage defects in the knee impair quality of life as much as severe osteoarthritis: a comparison of Knee Injury and Osteoarthritis Outcome Score in 4 patient categories scheduled for knee surgery. Am J Sports Med. 2010;38(2):231-7. doi:10.1177/0363546509352157. - DOI - PubMed
    1. Sanders TL, Pareek A, Obey MR, Johnson NR, Carey JL, Stuart MJ, et al.. High rate of osteoarthritis after osteochondritis dissecans fragment excision compared with surgical restoration at a mean 16-year follow-up. Am J Sports Med. 2017;45(8):1799-805. doi:10.1177/0363546517699846. - DOI - PubMed
    1. Everhart JS, Abouljoud MM, Kirven JC, Flanigan DC. Full-thickness cartilage defects are important independent predictive factors for progression to total knee arthroplasty in older adults with minimal to moderate osteoarthritis: data from the osteoarthritis initiative. J Bone Joint Surg Am. 2019;101(1):56-63. doi:10.2106/JBJS.17.01657. - DOI - PubMed
    1. Niemeyer P, Albrecht D, Andereya S, Angele P, Ateschrang A, Aurich M, et al.. Autologous chondrocyte implantation (ACI) for cartilage defects of the knee: a guideline by the working group “Clinical Tissue Regeneration” of the German Society of Orthopaedics and Trauma (DGOU). Knee. 2016;23(3):426-35. doi:10.1016/j.knee.2016.02.001. - DOI - PubMed
    1. Khella CM, Asgarian R, Horvath JM, Rolauffs B, Hart ML. An evidence-based systematic review of human knee post-traumatic osteoarthritis (PTOA): timeline of clinical presentation and disease markers, comparison of knee joint PTOA models and early disease implications. Int J Mol Sci. 2021;22(4):1996. doi:10.3390/ijms22041996. - DOI - PMC - PubMed

Publication types

Associated data