Comparison of Intra-Articular Injections of Plasma Rich in Growth Factors (PRGF-Endoret) Versus Durolane Hyaluronic Acid in the Treatment of Patients With Symptomatic Osteoarthritis: A Randomized Controlled Trial

doi:10.1016/j.arthro.2013.07.264

Arthroscopy: The Journal of Arthroscopic & Related Surgery

Volume 29, Issue 10, October 2013, Pages 1635-1643

https://doi.org/10.1016/j.arthro.2013.07.264 Get rights and content

Purpose

The purpose of this study was to compare the efficacy and safety in a randomized, clinical trial of 3 injections of PRGF-Endoret (BTI Biotechnology Institute, Vitoria, Spain) versus one single intra-articular injection of Durolane hyaluronic acid (HA) (Q-MED AB, Uppsala, Sweden) as a treatment for reducing symptoms in patients with knee osteoarthritis (OA).

Methods

Ninety-six patients with symptomatic knee OA were randomly assigned to receive PRGF-Endoret (3 injections on a weekly basis) or one infiltration with Durolane HA. The primary outcome measures were a 30% decrease and a 50% decrease in the summed score for the pain, physical function, and stiffness subscales of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Lequesne scores from baseline to weeks 24 and 48. The percentage of OMERACT-OARSI (Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative) responders was also documented. As secondary outcomes, pain, stiffness, and physical function by use of the WOMAC and the Lequesne score were considered and overall safety of the injection themselves.

Results

The mean age of the patients was 63.6 years. Treatment with PRGF-Endoret was significantly more efficient than treatment with Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA. The rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including pain, stiffness, and physical function on the WOMAC, Lequesne index, and OMERACT-OARSI responders at 24 and 48 weeks. Adverse events were mild and evenly distributed between the groups.

Conclusions

Our findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks; provides a significant clinical improvement, reducing patients' pain and improving joint stiffness and physical function with respect to basal levels in patients with knee OA; and should be considered in the treatment of patients with knee OA.

Level of Evidence

Level I, multicenter randomized controlled clinical trial.

Section snippets

Methods

The study was carried out in accordance with the international standards on clinical trials: Real Decreto (Royal Decree) 223/2004, Declaration of Helsinki in its latest revised version (Seoul, 2008), and Good Clinical Practice Regulations (International Conference for Harmonization). The study protocol was reviewed and approved by the reference ethics committee. All patients provided written informed consent before entry into the study.

Patient Characteristics

A total of 110 patients were initially screened, and 14 were excluded; thus 96 patients underwent randomization and treatment and completed the follow-up. The most common reason for exclusion (8 patients) was incomplete follow-up (Fig 1). The mean age was 63.6 years (range, 50 to 84 years), the mean body mass index was 30.9 (range, 20.7 to 42.9), and in both groups the percentage of women was higher (66.7% and 54.2% for PRGF-Endoret and HA groups, respectively). As shown in Table 3, the groups

Discussion

The results from this randomized trial show that the treatment based on 3 intra-articular injections of the autologous biological therapy, plasma rich in growth factors (PRGF-Endoret), is significantly more efficient than 1 single injection of Durolane HA in reducing knee pain and stiffness and improving physical function in patients with knee OA. In fact, the rate of response to PRGF-Endoret was significantly higher than the rate of response to HA for all the scores including the WOMAC pain,

Conclusions

Our findings show that PRGF-Endoret is safe and significantly superior to Durolane HA in primary and secondary efficacy analysis both at 24 and 48 weeks, and it provides a significant clinical improvement, reducing patients' pain and improving joint stiffness and physical function, with respect to basal levels in patients with knee OA. In addition, the efficacy of PRGF-Endoret has been shown in patients with Kellgren-Lawrence classification grade 2 to 4. Therefore we suggest that this

Acknowledgment

The authors thank Ester Montes, Verónica Moreno, and José Javier Aguirre for their contribution to this article. They also thank BTI Biotechnology Institute for its active contribution.

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Cited by (189)

Three Doses of Platelet-Rich Plasma Therapy Are More Effective Than One Dose of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis
2023, Arthroscopy - Journal of Arthroscopic and Related Surgery
To compare the efficacy of a single dose of platelet-rich plasma (PRP) with multiple doses of PRP therapy in the treatment of knee osteoarthritis (KOA).
The PubMed, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, and Cochrane Library databases were searched from database inception to May 2022; in addition, the gray literature and bibliographic references were searched. Only randomized controlled trials comparing the effect of a single dose versus multiple doses of PRP for KOA were included. Literature retrieval and data extraction were conducted by 3 independent reviewers. The inclusion and exclusion criteria were based on type of study, research subjects, intervention, outcome, language, and availability of data. Pooled analyses of visual analog scale (VAS) scores, Western Ontario and McMaster Universities Arthritis Index scores, and adverse events were conducted.
Seven studies (all randomized controlled trials) of high methodologic quality involving 575 patients were included. The ages of the patients included in this study ranged from 20 to 80 years, and the sex ratio was balanced. Triple-dose PRP therapy resulted in significantly better VAS scores compared with single-dose PRP therapy at 12 months (P < .0001), with no significant change in VAS scores between double-dose PRP and single-dose PRP at 12 months. Regarding adverse events, double-dose (P = .28) and triple-dose (P = .24) therapy showed no significant differences in safety from single-dose therapy.
Although there is a paucity of large high-quality Level I studies, current best evidence suggests that 3 doses of PRP for KOA are more effective than 1 dose of PRP at providing pain relief up to 1 year after administration.
Level II, systematic review of Level II studies.
Patients With Knee Osteoarthritis Who Receive Platelet-Rich Plasma or Bone Marrow Aspirate Concentrate Injections Have Better Outcomes Than Patients Who Receive Hyaluronic Acid: Systematic Review and Meta-analysis
2023, Arthroscopy - Journal of Arthroscopic and Related Surgery
To systematically review the literature to compare the efficacy and safety of platelet-rich plasma (PRP), bone marrow aspirate concentrate (BMAC), and hyaluronic acid (HA) injections for the treatment of knee osteoarthritis (OA).
A systematic review was performed by searching PubMed, the Cochrane Library, and Embase to identify Level I studies that compared the clinical efficacy of at least 2 of the following 3 injection therapies: PRP, BMAC, and HA for knee OA. The search phrase used was knee AND osteoarthritis AND randomized AND (“platelet rich plasma” OR “bone marrow aspirate” OR “hyaluronic acid”). Patients were primarily assessed based on patient-reported outcome scores (PROs) including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), visual analog scale (VAS) for pain, and Subjective International Knee Documentation Committee (IKDC) score.
Twenty-seven studies (all Level I) met inclusion criteria, including 1,042 patients undergoing intra-articular injection(s) with PRP (mean age 57.7 years, mean follow-up 13.5 months), 226 patients with BMAC (mean age 57.0 years, mean follow-up 17.5 months), and 1,128 patients with HA (mean age 59.0 years, mean follow-up 14.4 months). Nonnetwork meta-analyses demonstrated significantly better postinjection WOMAC (P < .001), VAS (P < .01), and Subjective IKDC scores (P < .001) in patients who received PRP compared with patients who received HA. Similarly, network meta-analyses demonstrated significantly better postinjection WOMAC (P < .001), VAS (P = .03), and Subjective IKDC (P < .001) scores in patients who received BMAC compared with patients who received HA. There were no significant differences in postinjection outcome scores when comparing PRP with BMAC.
Patients undergoing treatment for knee OA with PRP or BMAC can be expected to experience improved clinical outcomes when compared with patients who receive HA.
Level I, meta-analysis of Level I studies.
Serial intraarticular injections of growth factor concentrate in knee osteoarthritis: A placebo controlled randomized study
2023, Journal of Orthopaedics
To evaluate and compare clinical efficacy and effect on specific serum biomarker with serial injections of growth factor concentrate (GFC) for knee osteoarthritis (KOA) in a randomized triple blinded placebo controlled interventional study.
Final assessment was done on 58 patients. Patients with Kellgren-Lawrence grade II, III knee osteoarthritis were administered monthly intraarticular injections(3 injections) of GFC(n = 31) or saline(n = 27) and evaluated clinically with visual analogue scale(VAS) and Western Ontario and McMaster Universities Arthritis Index(WOMAC) at 3,6 and 12 months post therapy. Biochemical analysis was done with serum biomarker of cartilage degeneration, Collagen 2-1 (Coll2-1), estimated at baseline and at final follow up.
Both the groups exhibited statistically significant improvements (P < 0.05) in VAS at 3,6 and 12 months. WOMAC improvement reached statistical significance for GFC group at every evaluation (P < 0.001) but only at 12 months in NS group (P = 0.029). The improvements were clinically meaningful only in GFC group throughout follow up (Minimal clinically important differences >12% of baseline in WOMAC and >2 cm difference in mean for VAS). Intergroup comparison revealed GFC to be much better for both scores at every evaluation (95% CI of 0.2–1.5,[P = 0.008], 1.4–2.9,[P < 0.0001], and 2.7–4.2,[P < 0.0001] for VAS, 7.3–16.0 [P < 0.001], 11.6–21.9 [P < 0.001] and 18.1–31.1[P < 0.001] for WOMAC). Statistically significant decrease in serum Coll2-1 levels were observed for GFC group only. No serious complications were seen.
Serial(three) monthly GFC injections result in clinically meaningful improvement of subjective pain and function outcome scores, sustaining up to 12 months in KOA grade II and III. GFC also lead to significant reduction in serum levels of cartilage degradation biomarker coll2-1.
Office-Based Intraosseous Infiltrations of PRGF in Knee Osteoarthritis: Description of Technique
2022, Arthroscopy Techniques
Knee osteoarthritis is a low-degree inflammatory condition that involves the whole synovial joint tissues as an organ. Recently, a biological approach using plasma rich in growth factors (PRGF) to tackle not only the synovial joint with intraarticular injections of PRGF, but also the subchondral bone with intraosseous infiltrations has been implemented with promising results. However, this procedure requires sedation, which limits the implementation of the procedure to operating room. We propose a modified and less cumbersome PRGF intraosseous infiltration approach for moderate and severe knee osteoarthritis, conducting the procedure in the ambulatory setting assisted with WALANT (wide-awake local anesthesia no tourniquet) technique. The proposed technique with a minimally invasive local anesthesia involves subcutaneous infiltration of lidocaine and epinephrine in a solution without sedation, and using ultrasound guidance, thereby streamlining the original procedure. This procedure is both a cost-effective and safe approach that may contribute to the widespread use of intraosseous infiltrations.
A systematic review on the high variability in study design and outcome reporting in randomized controlled trials examining intra-articular platelet-rich plasma injection for knee osteoarthritis
2022, Journal of Cartilage and Joint Preservation
Prior literature has demonstrated variability in the preparation of platelet-rich plasma (PRP) for knee osteoarthritis, but it is unclear if study design and postoperative outcomes have been standardized for this intervention.
To determine the variability in study design and outcome reporting across randomized controlled trials (RCTs) examining intra-articular PRP injections for knee osteoarthritis.
The Cochrane Database, PubMed, EMBASE, and MEDLINE.
Level I and II RCTs examining intra-articular PRP injections for knee osteoarthritis were included.
The Jadad score was utilized.
Twenty-seven studies were included. Five studies conducted repeat imaging postoperatively. Visual Analog Scale (VAS) Pain (63%) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) (59.3%) were the 2 most utilized PROMs, followed by Knee Injury and Osteoarthritis Outcome Score (KOOS) (29.6%). Twelve (44%) RCTs reported 3 or more PROM (ie, VAS, KOOS, WOMAC). Most RCTs did not report objective outcome measures (70.4%).
The findings were largely descriptive in nature with limited utilization of statistical evaluation.
RCTs examining outcomes after intra-articular PRP injection for knee OA demonstrate substantial variability. Standardizing the population of most benefit with respect to arthritis grade may help in limiting population heterogeneity for future study comparison and pooling. In addition, PROs should be reported in a domain-specific manner allowing for assessment of pain, function, and health-related quality of life.
This review was not registered with PROSPERO.
II; Systematic Review of Level I-II RCTs.
Comparison of Minimally Invasive Procedures to Treat Knee Pain Secondary to Osteoarthritis: A Systematic Review and Meta-Analysis
2022, Journal of Vascular and Interventional Radiology
To review and indirectly compare the outcomes of genicular artery embolization (GAE), radiofrequency (RF) ablation, and intra-articular (IA) injection for the treatment of knee pain secondary to osteoarthritis (OA).
A literature review of the MEDLINE and Cochrane databases was conducted with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement in June 2020. The visual analog scale (VAS) was recorded at baseline and at all available time points for each therapy. Standard mean differences were calculated at each time point and compared between treatments to assess the magnitude of the treatment effect.
All 3 treatments demonstrated significant differences in VAS scores after therapy. RF ablation produced the greatest significant mean reduction in relative VAS score from baseline at 1 year of follow-up (mean, 0.49; 95% confidence interval, 0.4–0.59; P = .03). GAE reported the most significant reductions in VAS scores across all measured time points. Overall, the comparison did not demonstrate a significant difference in VAS scores among patients receiving IA injections, RF ablation, and GAE.
The current evidence does not suggest a significant difference in outcomes among IA injection, RF ablation, and GAE for knee pain secondary to OA.

View all citing articles on Scopus

: Supported by the Biomedical Research Foundation of Príncipe de Asturias University Hospital and Ministry of Health, Social Policy and Equality of Spain. The authors report the following source of funding: V.V., M.Á.P., I.A., R.S., G.O., and E.A. receive support from BTI.

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Original ArticleComparison of Intra-Articular Injections of Plasma Rich in Growth Factors (PRGF-Endoret) Versus Durolane Hyaluronic Acid in the Treatment of Patients With Symptomatic Osteoarthritis: A Randomized Controlled Trial

Purpose

Methods

Results

Conclusions

Level of Evidence

Section snippets

Methods

Patient Characteristics

Discussion

Conclusions

Acknowledgment

Lancet

Osteoarthritis Cartilage

Osteoarthritis Cartilage

Biomaterials

Adv Drug Deliv Rev

Arthroscopy

Osteoarthritis Cartilage

Osteoarthritis Cartilage

Pain

Eur J Pain

Arthroscopy

Osteoarthritis Cartilage

Osteoarthritis Cartilage

Restricted activity days among older adults

Am J Public Health

The effects of specific medical conditions on the functional limitation of elders in the Framingham Study

Am J Public Health

Original Article
Comparison of Intra-Articular Injections of Plasma Rich in Growth Factors (PRGF-Endoret) Versus Durolane Hyaluronic Acid in the Treatment of Patients With Symptomatic Osteoarthritis: A Randomized Controlled Trial