Original Article
Arthroscopic Subchondral Drilling Followed by Injection of Peripheral Blood Stem Cells and Hyaluronic Acid Showed Improved Outcome Compared to Hyaluronic Acid and Physiotherapy for Massive Knee Chondral Defects: A Randomized Controlled Trial

https://doi.org/10.1016/j.arthro.2021.01.067Get rights and content

Purpose

The purpose of this study was to evaluate the safety and efficacy of intra-articular injections of autologous peripheral blood stem cells (PBSCs) plus hyaluronic acid (HA) after arthroscopic subchondral drilling into massive chondral defects of the knee joint and to determine whether PBSC therapy can improve functional outcome and reduce pain of the knee joint better than HA plus physiotherapy.

Methods

This is a dual-center randomized controlled trial (RCT). Sixty-nine patients aged 18 to 55 years with International Cartilage Repair Society grade 3 and 4 chondral lesions (size ≥3 cm2) of the knee joint were randomized equally into (1) a control group receiving intra-articular injections of HA plus physiotherapy and (2) an intervention group receiving arthroscopic subchondral drilling into chondral defects and postoperative intra-articular injections of PBSCs plus HA. The coprimary efficacy endpoints were subjective International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS)–pain subdomain measured at month 24. The secondary efficacy endpoints included all other KOOS subdomains, Numeric Rating Scale (NRS), and Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores.

Results

At 24 months, the mean IKDC scores for the control and intervention groups were 48.1 and 65.6, respectively (P < .0001). The mean for KOOS-pain subdomain scores were 59.0 (control) and 86.0 (intervention) with P < .0001. All other KOOS subdomain, NRS, and MOCART scores were statistically significant (P < .0001) at month 24. Moreover, for the intervention group, 70.8% of patients had IKDC and KOOS-pain subdomain scores exceeding the minimal clinically important difference values, indicating clinical significance. There were no notable adverse events that were unexpected and related to the study drug or procedures.

Conclusions

Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement of clinical and radiologic scores compared with HA plus physiotherapy.

Level of Evidence

Level I, RCT.

Section snippets

Methods

This is a 24-month dual-center, open-label phase IIB randomized controlled trial (RCT) conducted as part of an Investigational New Drug application reviewed and cleared by the US Food and Drug Administration (IND 15993). Institutional review board approval was obtained from the Medical Research and Ethics Committee (Ministry of Health Malaysia) from the Malaysian site and the Baptist Hospital System of Pensacola, Florida, from the US site.

An independent data safety monitoring committee (DSMC)

Results

The protocol-defined interim analysis was performed and the results presented to the DSMC. Early closure of the study was recommended by the DSMC due to overwhelming statistical significance seen at 2 years in the absence of any safety concerns. Enrollment was halted in March 2020, and the study was therefore concluded prior to the recruitment of the 120 patients as originally designed.

At the point of halting study enrollment, the total recruited patients in this study were 81 (control, 38;

Discussion

The results of this RCT evaluating intra-articular injections of autologous PBSCs plus HA after arthroscopic subchondral drilling into massive chondral defects of the knee joint showed that this cartilage repair technique is safe and effective, with improved knee function and pain reduction better than HA plus physiotherapy. Improvements for the intervention group in the subjective IKDC (P < .0001) and KOOS-pain subdomain scores (P < .0001) were statistically significant at 24 months compared

Conclusions

Arthroscopic marrow stimulation with subchondral drilling into massive chondral defects of the knee joint followed by postoperative intra-articular injections of autologous PBSCs plus HA is safe and showed a significant improvement in clinical and radiologic scores as compared with HA plus physiotherapy.

Acknowledgment

This study is sponsored by KLSMC Stem Cells Inc and supported by grants from City of Gulf Breeze, Florida, and the State of Florida. The authors thank Dr Surinder Kaur, Ms Malar Muniandy, Ms Amal Mohd Dawam, Ms Alisha Ramlan, Ms Jocelyn Dowse, Ms Casandra Tan, and Mr Wai Choong Koh from Kuala Lumpur Medicine Centre, Malaysia; Dr Candace Anz, Dr Josh Hackel, Mr Johnny Torres, and Ms Mikala McMillion at the Andrews Research and Education Foundation, U.S.A.; and Dr Thong Chwee Ling, Dr Raja Kumar

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    The authors report the following potential conflicts of interest or sources of funding: This study is sponsored by KLSMC Stem Cells Inc and supported by grants from City of Gulf Breeze, Florida, and the State of Florida. Full ICMJE author disclosure forms are available for this article online, as supplementary material.

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