Single intra-articular injection with or without intra-osseous injections of platelet-rich plasma in the treatment of osteoarthritis knee: A single-blind, randomized clinical trial
BACKGROUND Subchondral bony structure damage plays an essential role in the pathogenesis of osteoarthritis (OA) knee. An intra-articular injection cannot reach the damaged subchondral bony structure and treat its pathologies effectively. The objective of the study was to compare the clinical effects of single intra-articular injection with or without intra-osseous injections of PRP in the treatment of osteoarthritis (OA) knee. METHODS This was a single-blind, parallel-group, randomized clinical trial. Fifty patients, with OA knee (K&L grade III), with ages between 50 and 65 years, were randomly allocated into 'intra-osseous, intra-articular PRP' ('IO+IA-PRP') (n = 25) or 'intra-articular PRP' group ('IA-PRP') (n = 25). Patients in the 'IO+IA-PRP' group received 18 ml PRP injection, and the 'IA-PRP' group received 8 ml PRP injection. Intra-osseous injections were given at the tibial plateau (5 ml) and femoral condyle (5 ml), along with intra-articular knee injection (8 ml), under fluoroscopic guidance. Outcomes were measured using VAS-pain, the knee injury and osteoarthritis outcome score (KOOS), and the treatment satisfaction scale. All patients (n = 50) were followed up till six months. RESULTS The mean age was 57.12(4.27) years and 57.00(4.96) years in the 'IO+IA-PRP' and 'IA-PRP' groups. Both groups showed significant improvement in pain relief (VAS pain) and KOOS parameters: pain, symptoms, ADL function, sport and recreation function, and quality of life. Compared to the 'IA-PRP' group, the 'IO+IA-PRP' group showed a greater reduction of VAS pain at six months. However, no significant difference was obtained in VAS pain-relief between these two groups (p = 0.422) at six months. Similarly, at 6 months, in inter-group comparison, except 'sport and recreation function' (p < 0.05), no significant differences were obtained in mean-scores of KOOS parameters: pain (p = 0.514); symptom (p = 0.148), ADL-function (p = 0.991), QoL-(p = 0.376). Patients in the 'IO+IA-PRP' group complained of significant 'injection-associated' adverse events and consumed a greater number of Acetaphenomen. CONCLUSIONS Both groups showed significant improvement following the intervention. Intra-osseous PRP injections did not provide any additional benefit over intra-articular PRP injection until six months regarding pain relief and functional improvement.
Safety and Efficacy of Platelet Rich Plasma for Treatment of Lumbar Discogenic Pain: A Prospective, Multicenter, Randomized, Double-blind Study
Pain physician. 2022;25(1):29-34
BACKGROUND Interventions for chronic discogenic spine pain are currently insufficient in lowering individual patient suffering and global disease burden. A 2016 study of platelet rich plasma (PRP) for chronic discogenic pain previously demonstrated clinically significant response among active group patients compared with controls. OBJECTIVES To replicate the previous research to move this intervention forward as a viable option for patient care. STUDY DESIGN A double-blind, randomized, placebo-controlled study. SETTING Multicenter private practices. METHODS Twenty-six (12 men, 14 women) human patients, ages 25 to 71 with a diagnosis of chronic lumbar discogenic pain, were randomly assigned to active (PRP) or control (saline) groups in a ratio of 2 active to 1 control. Baseline and follow-up Oswestry Disability Index and Numeric Pain Rating Scale questionnaires were obtained to track patient outcomes at 8 weeks postoperatively. RESULTS Within group assessment showed clinically significant improvement in 17% of PRP patients and clinically significant decline in 5% (1 patient) of the active group. Clinically significant improvement was seen in 13% of placebo group patients and no placebo patients had clinically significant decline secondary to the procedure. LIMITATIONS Possible explanations may include a range of factors including differences in patient demographics, outcome-measure sensitivity, or misalignment of statistical analyses. CONCLUSIONS These findings are markedly different than the highly promising results of the 2016 PRP study. This study posits necessary caution for researchers who wish to administer PRP for therapeutic benefit and may ultimately point to necessary redirection of interventional research for discogenic pain populations.
Efficacy of a Novel Intra-Articular Administration of Platelet-Rich Plasma One-Week Prior to Hyaluronic Acid versus Platelet-Rich Plasma Alone in Knee Osteoarthritis: A Prospective, Randomized, Double-Blind, Controlled Trial
Journal of clinical medicine. 2022;11(11)
Recent studies have suggested that the combined injection of platelet-rich plasma (PRP) and hyaluronic acid (HA) may have additive benefits for knee osteoarthritis over PRP alone, but there is insufficient evidence to support this combined injection. Moreover, the simultaneous injection of PRP and HA may offset the combined effect. Hence, the aim of this prospective, randomized, double-blind study was to assess their combined efficacy with a novel injection protocol. Forty-six study subjects with unilateral knee osteoarthritis were randomized to receive either a single-dose injection of HA (intervention group) or normal saline (control group) 1 week after a single-dose injection of leukocyte-poor PRP. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and static balance and the risk of falls measured by Biodex Balance System were, respectively, the primary and secondary outcome measures. Evaluations were performed at baseline, 1 month, 3 months, 6 months, and 12 months post-injection. The intervention group exhibited significant declines in WOMAC pain, stiffness, and total scores, as well as static balance, compared to the control group (p < 0.05). These randomized double-blind control trials, with novel protocol of intra-articular injection of PRP 1-week prior to HA, provide greater symptom relief and improve static balance compared to PRP alone in patients with knee osteoarthritis.
No Benefit to Platelet-rich Plasma Over Placebo Injections in Terms of Pain or Function in Patients with Hemophilic Knee Arthritis: A Randomized Trial
Clinical orthopaedics and related research. 2022
BACKGROUND Hemophilic knee arthritis is one of the most common presenting symptoms of hemophilia, and its management continues to be challenging to practitioners. Preliminary research has suggested that platelet-rich plasma (PRP) may have short-term efficacy in the treatment of hemophilic knee arthritis, but evidence for this treatment is limited. QUESTIONS/PURPOSES What is the effectiveness of PRP compared with placebo in (1) reducing pain and improving knee joint function (as measured by WOMAC, VAS, and Hemophilia Joint Health Score [HJHS]) and (2) improving quality of life (as measured by SF-36 scores) in patients with hemophilic knee arthritis through 24 months of follow-up? METHODS This was a prospective, parallel-group, double-blinded, single-center, placebo-controlled randomized clinical trial that included participants from a tertiary care center starting January 1, 2019, with follow-up completed on November 30, 2021. Participants were older than 18 years and had hemophilic knee arthritis confirmed by MRI, and they were randomly allocated to interventions in a 1:1 ratio. The investigators were not informed of the randomization sequence generated by the computer. Patient groups were comparable with respect to age, gender, BMI, hemophilia type, and disease severity at baseline. Physicians delivered three sessions (one per week) of a standard intraarticular injection of PRP (n = 95) or placebo (n = 95). The rate of successful blinding was balanced across the groups, which was assessed by asking participants which injection they thought they had received. The primary outcome was the WOMAC score (range 0 to 96; higher scores indicate more pain and worse function; minimum clinically important difference, 6.4 points) over 24 months. Among the 190 patients assigned to PRP or saline injections (mean age 31 ± 7 years), 100% (190) of patients were men). There was no between-group difference in the proportion of patients who completed the trial; 97% (92 of 95) of patients in the PRP group and 94% (89 of 95) of patients in the placebo group completed the trial. The most common adverse events were injection site discomfort 8% (8 of 95) in the PRP group and 4% (4 of 95) in the placebo group. An intention-to-treat analysis was planned, but there was no crossover between groups. All patients were included in the analyses. With 95 patients in each group, the study was powered a priori at 90% to detect a difference in WOMAC score of 6.4 points, which was considered a clinically important difference. RESULTS There were no clinically important differences in the mean WOMAC, VAS pain, HJHS, SF-36, and MRI scores between groups at any timepoint. Intraarticular PRP did not ameliorate function, symptoms, and quality of life in patients with hemophilic knee arthritis. At 24 months of follow-up, the mean difference between the PRP and placebo groups in the WOMAC score was -1 (95% CI -5 to 2; p = 0.42). The mean difference in the VAS pain score was -0.3 (95% CI -0.8 to 0.2; p = 0.19), in the HJHS was -0.6 (95% CI -1.4 to 0.1; p = 0.10), in the SF-36 physical component summary was 0 (95% CI -2 to 3; p = 0.87), and in the SF-36 mental component summary was -1 (95% CI -3 to 2; p = 0.64). The mean differences in the MRI scores of soft tissue and osteochondral subscore were 0.1 (95% CI -0.3 to 0.5; p = 0.59) and -0.3 (95% CI -0.7 to 0.1; p = 0.19), respectively. CONCLUSION Among patients with hemophilic knee arthritis, three intraarticular PRP injections, compared with placebo injections, did not improve hemophilic knee symptoms, function, and quality of life over 24 months. The results of this study do not support the use of PRP injections in patients who have hemophilic knee arthritis. LEVEL OF EVIDENCE Level I, therapeutic study.
Allogeneic platelet-derived growth factors local injection in treatment of tennis elbow: a prospective randomized controlled study
International orthopaedics. 2022
PURPOSE The purpose of this study aimed to evaluate the efficacy of local injection of allogeneic platelet-derived growth factors in treatment of patients with tennis elbow. PATIENTS AND METHODS This study included 120 tennis elbow patients randomly divided into two groups. The patients were locally injected with allogeneic growth factors (treatment group) or with normal saline (control group). The outcomes were assessed using Patient-Related Tennis Elbow Evaluation (PRTEE) and quick Disabilities of the Arm, Shoulder and Hand (qDASH) scales. The clinical outcomes were accordingly classified as excellent, good and poor. The patient's satisfaction and adverse effects were also recorded. RESULTS There was no statistically significant difference between the two groups regarding the age, gender, dominant arm or the pre-injection scores. At three month follow-up, the reductions in the mean PRTEE and qDASH scores were 88.7% and 70.6% in the treatment group versus 21.8% and 14.9% in the control group, respectively. At the last follow-up, the outcomes in the treatment group were excellent in 85% of patients and good in 15%, versus 8% and 32% in the control group. Overall, 95% were satisfied in the treatment group compared to 25% in control group. Forty patients in the treatment group experienced mild transient post-injection pain. CONCLUSION This study strongly suggests that local injection of allogeneic platelet-derived growth factors could be a promising safe treatment option for tennis elbow with significant pain relief, functional improvement and patient's satisfaction. Yet, additional larger studies are needed to assess the durability of these outcomes.
Efficacy of Ultrasound-Guided Glenohumeral Joint Injections of Leukocyte-Poor Platelet-Rich Plasma Versus Hyaluronic Acid in the Treatment of Glenohumeral Osteoarthritis: A Randomized, Double-Blind Controlled Trial
Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine. 2022
OBJECTIVE To compare the efficacy of ultrasound-guided hyaluronic acid (HA) versus leukocyte-poor platelet-rich plasma (LP-PRP) injection in the treatment of glenohumeral osteoarthritis. DESIGN Double-blind randomized controlled trial. SETTING Academic institution. PATIENTS Seventy patients with chronic glenohumeral osteoarthritis were randomly assigned to receive a single injection of HA (n = 36) or LP-PRP (n = 34). INTERVENTIONS Leukocyte-poor platelet-rich plasma was processed using Harvest/TerumoBCT Clear PRP kits. Ultrasound-guided injections of 6 mL HA or 6 mL LP-PRP into the glenohumeral joint were performed. Patients, the injecting physician, and outcomes assessor were blinded to treatment assignments. MAIN OUTCOME MEASURES Shoulder Pain and Disability Index (SPADI), American Shoulder and Elbow Surgeons (ASES) score, current/average numerical rating scale (NRS) pain scores, satisfaction, and side effects were assessed at the 5 follow-up time points over 12 months. RESULTS Baseline characteristics were similar between groups. There were no significant between-group differences regarding SPADI, ASES, and current/average NRS pain scores at any time point up to 12 months postinjection (P > 0.05). However, significant improvements in SPADI, ASES, and current/average NRS pain scores were observed in both groups starting at 1 or 2 months (P < 0.01, P < 0.01, P < 0.001, and P < 0.01, respectively). These improvements were observed regardless of osteoarthritis severity. For patients who received LP-PRP, there was no effect of platelet yield on outcomes. Side effect and satisfaction rates were similar between groups. CONCLUSIONS There were no differences in pain and functional outcomes after a single injection of LP-PRP versus HA. However, significant improvements in pain and function were observed after both treatments in patients with glenohumeral osteoarthritis.
Intra-articular injections of platelet-rich plasma decrease pain and improve functional outcomes than sham saline in patients with knee osteoarthritis
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. 2022
PURPOSE To compare the long-term clinical efficacy provided by intra-articular injections of either Pure Platelet-rich Plasma (P-PRP) or sham saline to treat knee osteoarthritis (KOA). METHODS This prospective, parallel-group, double-blind, multi-center, sham-controlled randomized clinical trial recruited participants with KOA from orthopedic departments at nine public hospitals (five tertiary medical centers, four secondary medical units) starting January 1, 2014, with follow-up completed on February 28, 2021. Participants were randomly allocated to interventions in a 1:1 ratio. Data were analyzed from March 1, 2021, to July 15, 2021. Three sessions (1 every week) of P-PRP or sham saline injected by physicians. The primary outcome was the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 3, 6, 12, 24, 60 months of follow-up. Secondary outcomes included the International Knee Documentation Committee (IKDC) subjective score, visual analogue scale (VAS) score, intra-articular biochemical marker concentrations, cartilage volume, and adverse events. Laboratory of each hospital analyzed the content and quality of P-PRP. RESULTS 610 participants (59% women) with KOA who received three sessions of P-PRP (n = 308, mean age 53.91 years) or sham saline (n = 302, mean age 54.51 years) injections completed the trial. The mean platelet concentration in PRP is 4.3-fold (95% confidence interval 3.6-4.5) greater than that of whole blood. Both groups showed significant improvements in IKDC, WOMAC, and VAS scores at 1 month of follow-up. However, only the P-PRP group showed a sustained improvement in clinical outcome measurements at month 24 (P < 0.001). There were statistically significant differences between the P-PRP and sham saline groups in all clinical outcome measurements at each follow-up time point (P < 0.001). The benefit of P-PRP was clinically better in terms of WOMAC-pain, WOMAC-physical function and WOMAC-total at 6, 12, 24, and 60 months of follow-up. No clinically significant differences between treatments were documented in terms of WOMAC-stiffness at any follow-up. A clinically significant difference favoring P-PRP group against saline in terms of IKDC and VAS scores was documented at 6, 12, 24 and 60 months of follow-up. At 6 months after injection, TNF-α and IL-1β levels in synovial fluid were lower in the P-PRP group (P < 0.001). Tibiofemoral cartilage volume decreased by a mean value of 1171 mm(3) in the P-PRP group and 2311 mm(3) in the saline group over 60 months and the difference between the group was statistically significant (intergroup difference, 1140 mm(3), 95% CI - 79 to 1320 mm(3); P < 0.001). CONCLUSIONS In this randomized clinical trial of patients with KOA, P-PRP was superior to sham saline in treating KOA. P-PRP was effective for achieving at least 24 months of symptom relief and slowing the progress of KOA, with both P-PRP and saline being comparable in safety profiles.
Intra-articular injection with platelet-rich plasma compared to triamcinolone hexacetonide or saline solution in knee osteoarthritis: A double blinded randomized controlled trial with one year follow-up
Clinical rehabilitation. 2022;:2692155221090407
OBJECTIVES To compare the effectiveness of intra-articular injection (IAI) of Platelet-Rich Plasma (PRP) with Triamcinolone Hexacetonide (TH) and Saline Solution (SS), in patients with knee osteoarthritis (OA). DESIGN A randomized controlled trial, with blinded patients and assessor. SETTING Outpatient rheumatology service. SUBJECTS Patients with knee osteoarthritis grades II and III. INTERVENTIONS Patients received IAI with PRP, 40 mg TH, or SS. METHODS Patients were assessed at baseline and after 4, 8, 12 e 52 weeks with: visual analogue scale (VAS) for pain at rest and movement, WOMAC questionnaire, Timed to Up and Go test, 6-min walk test, percentage of improvement, goniometry, quality of life SF-36 questionnaire, Likert scale and Kelgreen & Lawrence (KL) radiographic scale (only at baseline and 52 weeks). RESULTS 100 patients were studied, with a mean age of 67.13(6.56) years. The TH group was superior for: percentage of improvement (versus SS group from 4 to 52 weeks); WOMAC total and pain (versus PRP group at 4 weeks); and WOMAC stiffness (versus SS group at 12 weeks). The SS group was inferior for WOMAC function (from 8 to 52 weeks). The PRP group showed lowest radiographic progression [TH 17 (51.51%) to 24 (72.72%); SS 17 (51.51%) to 30 (90.90%); PRP 20 (58.82%) to 21 (61.76%)]. CONCLUSION The Triamcinolone Hexacetonide group was superior for percentage of improvement and WOMAC, pain and stiffness. For the WOMAC function, the Platelet-Rich Plasma group and Triamcinolone Hexacetonide group were superior to the Saline group. The Platelet-Rich Plasma group showed the lowest radiographic progression at 52 weeks of follow-up.
Comparisons of Ultrasound-Guided Platelet-Rich Plasma Intra-Articular Injection and Extracorporeal Shock Wave Therapy in Treating ARCO I-III Symptomatic Non-Traumatic Femoral Head Necrosis: A Randomized Controlled Clinical Trial
Journal of pain research. 2022;15:341-354
BACKGROUND AND OBJECTIVE Osteonecrosis of the femoral head (ONFH) is a devastating disease, and there is some evidence that extracorporeal shock wave therapy (ESWT) and intra-articular platelet-rich plasma (PRP) injection might alleviate pain and improve joint function in individuals with ONFH. The objective of this study was to compare the effectiveness and safety of PRP and ESWT in symptomatic ONFH patients. METHODS A total of 60 patients aged 40-79 with unilateral ONFH at Association Research Circulation Osseous (ARCO) stages I, II, and III were randomly assigned to the PRP (N=30) or the ESWT group (N=30). Four treatment sessions were provided in both groups. Assessments were performed at baseline, and 1-, 3-, 6-, and 12-month. Primary outcomes were measured by the visual analogue scale (VAS), and pressure pain thresholds (PPTs). Secondary outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and magnetic resonance imaging (MRI). The linear mixed-model analysis was used to evaluate the differences between groups and within groups and the "group by time" interaction effects. RESULTS There were significant differences between groups in terms of changes over time for VAS, PPTs, WOMAC, and HHS since 3-month and maintained up to 12-month (P<0.05, except for PPTs at 12-month). The simple main effects showed that the patients in PRP group had greater improvements in VAS (mean difference = -0.82, 95% CI [-1.39, -0.25], P=0.005), WOMAC (mean difference = -4.19, 95% CI [-7.00, -1.37], P=0.004), and HHS (mean difference = 5.28, 95% CI [1.94, 8.62], P=0.002). No related adverse events were reported. CONCLUSION This study supported the effectiveness and safety of both the PRP injection and ESWT in treating ONFH patients. For symptomatic patients with ONFH, intra-articular PRP injection appeared superior to ESWT in pain relief and functional improvement.
Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial
The American journal of sports medicine. 2022;:3635465211064303
BACKGROUND Platelet-rich plasma (PRP) is gaining large interest in clinical practice as a minimally invasive injective treatment for knee osteoarthritis (OA). Different preparation methods are available, and the presence of leukocytes, deemed detrimental in some preclinical studies, is one of the most debated aspects regarding PRP efficacy. PURPOSE To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS A total of 192 patients with symptomatic knee OA (Kellgren-Lawrence grade 1-3) were randomly allocated to 3 weekly injections of LR-PRP or LP-PRP. LP-PRP was obtained with a filter for leukodepletion. LR-PRP and LP-PRP were divided into aliquots of 5 mL, with a mean platelet concentration of 1146.8 × 10(9)/L and 1074.9 × 10(9)/L and a mean leukocyte concentration of 7991.4 × 10(6)/L and 0.1 × 10(6)/L, respectively. Patients were evaluated at baseline and thereafter at 2, 6, and 12 months for the primary outcome, the International Knee Documentation Committee (IKDC) subjective score; and for secondary outcomes, the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol-visual analog scale (EQ-VAS), and Tegner score. RESULTS No differences between groups were observed in terms of absolute values or improvement of the clinical scores across all follow-up intervals. The mean IKDC subjective score at baseline and 12 months improved from 45.6 to 60.7 in the LR-PRP group as compared with 46.8 to 62.9 in the LP-PRP group (P = .626). No severe adverse events were described in either group, although 15 mild adverse events (knee pain or swelling) were reported: 12.2% for LR-PRP and 4.7% for LP-PRP (P = .101). No statistically significant difference was also found between LR-PRP and LP-PRP in terms of failures (7.8% vs 3.5%, P = .331). CONCLUSION This double-blind randomized trial showed that 3 intra-articular LR-PRP or LP-PRP injections produced similar clinical improvement in the 12 months of follow-up in patients with symptomatic knee OA. Both treatment groups reported a low number of adverse events, without intergroup differences. The presence of leukocytes did not significantly affect the clinical results of PRP injections. REGISTRATION NCT02923700 (ClinicalTrials.gov identifier).