The comparison effects of intra-articular injection of Platelet Rich Plasma (PRP), Plasma Rich in Growth Factor (PRGF), Hyaluronic Acid (HA), and ozone in knee osteoarthritis; a one year randomized clinical trial

Abstract Background Our study compare the short and long-term efficacy of the intra articular injections (IAIs) of hyaluronic acid (HA), platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), and ozone in patients with knee osteoarthritis (OA). Methods In this randomized clinical trial, 238 patients with mild to moderate knee OA were randomized into 4 groups of IAIs: HA (3 doses weekly), PRP (2 doses with 3 weeks interval), PRGF (2 doses with 3 weeks interval), and Ozone (3 doses weekly). Our outcome measures were the mean changes from baseline (immediately from the first injections) until 2,6, and 12 months post intervention in scores of visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. Results A total of 200 patients enrolled in the final analysis. The mean age of patients was 56.9 ± 6.3 years, and 69.5% were women. In 2 months follow up, significant improvement of pain, stiffness, and function were seen in all groups compared to the baseline, but the ozone group had the best results (P < 0.05). In 6 month follow up HA, PRP, and PRGF groups demonstrated better therapeutic effects in all scores in comparison with ozone (P < 0.05). At the end of the 12th month, only PRGF and PRP groups had better results versus HA and ozone groups in all scores (P < 0.05). Despite the fact that ozone showed better early results, its effects begin to wear off earlier than other products and ultimately disappear in 12 months. Conclusions Ozone injection had rapid effects and better short-term results after 2 months, but its therapeutic effects did not persist after 6 months and at the 6-month follow up, PRP,PRGF and HA were superior to ozone. Only patients in PRP and PRGF groups improved symptoms persisted for 12 months. Therefore, these products could be the preferable choices for long-term management. Trial registration Registered in the Iranian Center of Clinical Trials (www.irct.ir) in 11/11/2017 with the following code: IRCT2017082013442N17.

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AB0878 THE COMPARISON EFFECTS OF INTRA-ARTICULAR INJECTION OF PLATELET RICH PLASMA (PRP), PLASMA RICH IN GROWTH FACTOR (PRGF), HYALURONIC ACID (HA), AND OZONE IN KNEE OSTEOARTHRITIS; A ONE YEAR RANDOMIZED CLINICAL TRIAL

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.513 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1744.3-1745

Author(s):

S. A. Raeissadat ◽

P. Ghazi Hosseini ◽

M. H. Bahrami ◽

R. Salman Roghani ◽

M. Fathi ◽

...

Keyword(s):

Clinical Trial ◽

Knee Osteoarthritis ◽

Randomized Clinical Trial ◽

Platelet Rich Plasma ◽

Therapeutic Effects ◽

Short Term ◽

Knee Oa ◽

The Mean

Background:Knee osteoarthritis (OA) as a common progressive degenerative condition is one of the most important leading causes of disability and relative dependence. Worldwide prevalence of symptomatic knee OA has estimated 3.8%. It affects more than 20% of over 45-year-old population. Among the minimally invasive methods recommended for knee OA management is intra-articular injections for which a large array of products have been used. Despite all the existing options, there is still no general consensus on the choice and priority of the best intra-articular injection in knee osteoarthritis.Objectives:Our study compare the short and long-term efficacy of the intra articular injections (IAIs) of hyaluronic acid (HA), platelet-rich plasma (PRP), plasma rich in growth factors (PRGF), and ozone in patients with knee osteoarthritis (OA).Methods:In this single-blinded randomized clinical trial, 238 patients with mild to moderate knee OA were randomized into4 groups of IAIs: HA (3 doses weekly), PRP (2 doses with 3 weeks interval), PRGF (2 doses with 3 weeks interval), and Ozone (3 doses weekly). Our outcome measures were the mean changes from baseline until 2,6, and 12 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index.Results:A total of 200 patients enrolled final analysis. The mean age of patients was 56.9 ± 6.3 years, and69.5% were women. In 2 months follow up, significant improvement of pain, stiffness, and function were seen in all groups compared to the baseline, but the ozone group had the best results(P<0.05). In 6 month follow up HA, PRP, and PRGF groups demonstrated better therapeutic effects in all scores in comparison with ozone (P<0.05).At the end of the 12th month, only PRGF and PRP groups had better results versus HA and ozone groups in all scores (P<0.05).Despite the fact that ozone showed better early results, its effects begin to wear off earlier than other products and ultimately disappear in 12 months.Conclusion:Ozone injection had rapid effects and better short-term results after 2 months, but its therapeutic effects did not persist after 6 months and at the 6-month follow up, PRP,PRGF and HA were superior to ozone. Only patients in PRP and PRGF groups improved symptoms persisted for 12 months. Therefore, these products could be the preferable choices for long-term management.References:[1]Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cuscó X, Garcia-Balletbó M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Archives of orthopaedic and trauma surgery. 2011;131(3):311-7.[2]De La Mata J. Platelet rich plasma.A new treatment tool for the rheumatologist?ReumatologíaClínica (English Edition). 2013;9(3):166-71.[3]Raeissadat SA, Rayegani SM, Sedighipour L, Bossaghzade Z, Abdollahzadeh MH, Nikray R, et al. The efficacy of electromyographic biofeedback on pain, function, and maximal thickness of vastus medialis oblique muscle in patients with knee osteoarthritis: a randomized clinical trial. Journal of pain research. 2018;11:2781.[4]Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, Deyo RA, et al. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States: Part II. Arthritis & Rheumatism. 2008;58(1):26-35.[5]Tehrani-Banihashemi A, Davatchi F, Jamshidi AR, Faezi T, Paragomi P, Barghamdi M. Prevalence of osteoarthritis in rural areas of I ran: a WHO-ILAR COPCORD study. International journal of rheumatic diseases. 2014;17(4):384-8.[6]Rayegani SM, Raeissadat SA, Heidari S, Moradi-Joo M. Safety and effectiveness of low-level laser therapy in patients with knee osteoarthritis: a systematic review and meta-analysis. Journal of lasers in medical sciences. 2017;8(Suppl 1):S12.Disclosure of Interests:None declared

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Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis

10.21203/rs.3.rs-23831/v3 ◽

2020 ◽

Author(s):

José María Lamo-Espinosa ◽

Juan F. Blanco ◽

Mikel Sánchez ◽

Victoria Moreno ◽

Froilán Granero-Moltó ◽

...

Keyword(s):

Clinical Trial ◽

Bone Marrow ◽

Clinical Trials ◽

Knee Osteoarthritis ◽

Phase Ii ◽

Stromal Cells ◽

Platelet Rich Plasma ◽

X Ray ◽

The Mean

Abstract Background: Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100x106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial.Methods: A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100x106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage.Results: No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p=0.389) and from 5.3 (1.9) to 3.5 (2.5) (p=0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p=0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p=0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage.Conclusions: Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23

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Phase II multicenter randomized controlled clinical trial on the efficacy of intra-articular injection of autologous bone marrow mesenchymal stem cells with platelet rich plasma for the treatment of knee osteoarthritis

Journal of Translational Medicine ◽

10.1186/s12967-020-02530-6 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

José María Lamo-Espinosa ◽

Juan F. Blanco ◽

Mikel Sánchez ◽

Victoria Moreno ◽

Froilán Granero-Moltó ◽

...

Keyword(s):

Clinical Trial ◽

Bone Marrow ◽

Clinical Trials ◽

Knee Osteoarthritis ◽

Stromal Cells ◽

Platelet Rich Plasma ◽

Joint Damage ◽

X Ray ◽

The Mean

Abstract Background Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial. Methods A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. Results No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although statistical significances between groups have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. Conclusions Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy. Trial registration Clinical Trials.gov identifier NCT02365142. Nº EudraCT: 2011-006036-23

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Efficacy of Intra-articular Injection of a Newly Developed Plasma Rich in Growth Factor (PRGF) Versus Hyaluronic Acid on Pain and Function of Patients with Knee Osteoarthritis: A Single-Blinded Randomized Clinical Trial

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.1177/1179544117733452 ◽

2017 ◽

Vol 10 ◽

pp. 117954411773345 ◽

Cited By ~ 17

Author(s):

Seyed Ahmad Raeissadat ◽

Seyed Mansoor Rayegani ◽

Azadeh Gharooee Ahangar ◽

Porya Hassan Abadi ◽

Parviz Mojgani ◽

...

Keyword(s):

Clinical Trial ◽

Hyaluronic Acid ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Randomized Clinical Trial ◽

Repeated Measures ◽

Significant Difference ◽

Within Subjects ◽

The Mean ◽

And Function

Background and objectives: Knee osteoarthritis is the most common joint disease. We aimed to compare the efficacy and safety of intra-articular injection of a newly developed plasma rich in growth factor (PRGF) versus hyaluronic acid (HA) on pain and function of patients with knee osteoarthritis. Methods: In this single-blinded randomized clinical trial, patients with symptomatic osteoarthritis of knee were assigned to receive 2 intra-articular injections of our newly developed PRGF in 3 weeks or 3 weekly injections of HA. Our primary outcome was the mean change from baseline until 2 and 6 months post intervention in scores of visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Lequesne index. We used analysis of variance for repeated-measures statistical test. Results: A total of 69 patients entered final analysis. The mean age of patients was 58.2 ± 7.41 years and 81.2% were women. In particular, total WOMAC index decreased from 42.9 ± 13.51 to 26.8 ± 13.45 and 24.4 ± 16.54 at 2 and 6 months in the newly developed PRGF group (within subjects P = .001), and from 38.8 ± 12.62 to 27.8 ± 11.01 and 27.4 ± 11.38 at 2 and 6 months in the HA group (within subjects P = .001), respectively (between subjects P = .631). There was no significant difference between PRGF and HA groups in patients’ satisfaction and minor complications of injection, whereas patients in HA group reported significantly lower injection-induced pain. Conclusions: In 6 months follow up, our newly developed PRGF and HA, both are effective options to decrease pain and improvement of function in patients with symptomatic mild to moderate knee osteoarthritis.

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Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis

10.21203/rs.3.rs-23831/v1 ◽

2020 ◽

Author(s):

José María Lamo-Espinosa ◽

Juan F. Blanco ◽

Mikel Sánchez ◽

Victoria Moreno ◽

Froilán Granero-Moltó ◽

...

Keyword(s):

Clinical Trial ◽

Bone Marrow ◽

Clinical Trials ◽

Knee Osteoarthritis ◽

Stromal Cells ◽

Platelet Rich Plasma ◽

Joint Damage ◽

X Ray ◽

The Mean

Abstract Background Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100 × 106 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF®) as adjuvant in a randomized clinical trial. Methods A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF® or intraarticular administration of 100 × 106 cultured autologous BM-MSCs plus PRGF®. Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. Results No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF® and BM-MSC with PRGF® went from 5 (1.8) to 4.5 (2.2) (p = 0.389) and from 5.3 (1.9) to 3.5 (2.5) (p = 0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF® was 31.9 (16.2) and 22.3 (15.8) respectively (p = 0.002) while that for patients treated with BM-MSC plus PRGF® was 33.4 (18.7) and 23.0 (16.6) (p = 0.053). Although between groups statistically significances have been not detected, only patients being treated with BM-MSC plus PRGF® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. Conclusions Treatment with BM-MSC associated with PRGF® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy.

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Phase II Multicenter Randomized Controlled Clinical Trial on the Efficacy of Intra-articular Injection of Autologous Bone Marrow Mesenchymal Stem Cells with Platelet Rich Plasma for the Treatment of Knee Osteoarthritis

10.21203/rs.3.rs-23831/v2 ◽

2020 ◽

Author(s):

José María Lamo-Espinosa ◽

Juan F. Blanco ◽

Mikel Sánchez ◽

Victoria Moreno ◽

Froilán Granero-Moltó ◽

...

Keyword(s):

Clinical Trial ◽

Bone Marrow ◽

Clinical Trials ◽

Knee Osteoarthritis ◽

Stromal Cells ◽

Platelet Rich Plasma ◽

Joint Damage ◽

X Ray ◽

The Mean

Abstract Background Mesenchymal stromal cells are a safe and promising option to treat knee osteoarthritis as previously demonstrated in different clinical trials. However, their efficacy, optimal dose and addition of adjuvants must be determined. Here, we evaluated the clinical effects of a dose of 100x10 6 bone marrow mesenchymal stromal cells (BM-MSCs) in combination with Platelet Rich Plasma (PRGF ® ) as adjuvant in a randomized clinical trial. Methods A phase II, multicenter, randomized clinical trial with active control was conducted. Sixty patients diagnosed with knee OA were randomly assigned to 3 weekly doses of PRGF ® or intraarticular administration of 100x10 6 cultured autologous BM-MSCs plus PRGF ® . Patients were followed up for 12 months, and pain and function were assessed using VAS and WOMAC and by measuring the knee range of motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. Results No adverse effects were reported after BM-MSC administration or during follow-up. According to VAS, the mean value (SD) for PRGF ® and BM-MSC with PRGF ® went from 5 (1.8) to 4.5 (2.2) (p=0.389) and from 5.3 (1.9) to 3.5 (2.5) (p=0.01), respectively at 12 months.. In WOMAC, the mean (SD) baseline and 12-month overall WOMAC scores in patients treated with PRGF ® was 31.9 (16.2) and 22.3 (15.8) respectively (p=0.002) while that for patients treated with BM-MSC plus PRGF ® was 33.4 (18.7) and 23.0 (16.6) (p=0.053). Although between groups statistically significances have been not detected, only patients being treated with BM-MSC plus PRGF ® could be considered as a OA treatment responders following OARSI criteria. X-ray and MRI (WORMS protocol) revealed no changes in knee joint space width or joint damage. Conclusions Treatment with BM-MSC associated with PRGF ® was shown to be a viable therapeutic option for osteoarthritis of the knee, with clinical improvement at the end of follow-up. Further phase III clinical trials would be necessary to confirm the efficacy.

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Platelet-Rich Plasma-Derived Growth Factor vs Hyaluronic Acid Injection in the Individuals with Knee Osteoarthritis: A One Year Randomized Clinical Trial

Journal of Pain Research ◽

10.2147/jpr.s210715 ◽

2020 ◽

Vol Volume 13 ◽

pp. 1699-1711 ◽

Cited By ~ 1

Author(s):

Seyed Ahmad Raeissadat ◽

Azadeh Gharooee Ahangar ◽

Seyed Mansoor Rayegani ◽

Mohammadreza Minator Sajjadi ◽

Adel Ebrahimpour ◽

...

Keyword(s):

Clinical Trial ◽

Hyaluronic Acid ◽

Growth Factor ◽

Knee Osteoarthritis ◽

Randomized Clinical Trial ◽

Platelet Rich Plasma ◽

Hyaluronic Acid Injection ◽

Acid Injection ◽

One Year

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Knee Osteoarthritis Injection Choices: Platelet- Rich Plasma (PRP) versus Hyaluronic Acid (A one-year randomized clinical trial)

Clinical Medicine Insights Arthritis and Musculoskeletal Disorders ◽

10.4137/cmamd.s17894 ◽

2015 ◽

Vol 8 ◽

pp. CMAMD.S17894 ◽

Cited By ~ 121

Author(s):

Seyed Ahmad Raeissadat ◽

Seyed Mansoor Rayegani ◽

Hossein Hassanabadi ◽

Mohammad Fathi ◽

Elham Ghorbani ◽

...

Keyword(s):

Quality Of Life ◽

Clinical Trial ◽

Hyaluronic Acid ◽

Knee Osteoarthritis ◽

Randomized Clinical Trial ◽

Platelet Rich Plasma ◽

Healing Process ◽

Knee Oa ◽

Sf 36

Introduction Knee osteoarthritis (OA) is the most common articular disease. Different methods are used to alleviate the symptoms of patients with knee OA, including analgesics, physical therapy, exercise prescription, and intra-articular injections (glucocorticoids, hyaluronic acid [HA], etc). New studies have focused on modern therapeutic methods that stimulate cartilage healing process and improve the damage, including the use of platelet-rich plasma (PRP) as a complex of growth factors. Due to the high incidence of OA and its consequences, we decided to study the long-term effect of intraarticular injection of PRP and HA on clinical outcome and quality of life of patients with knee OA. Method This non-placebo-controlled randomized clinical trial involved 160 patients affected by knee OA, grade 1–4 of Kellgren–Lawrence scale. In the PRP group ( n = 87), two intra-articular injections at 4-week interval were applied, and in the HA group ( n = 73), three doses of intra-articular injection at 1-week interval were applied. All patients were prospectively evaluated before and at 12 months after the treatment by Western Ontario and McMaster Universities Arthritis Index (WOMAC) and SF-36 questionnaires. The results were analyzed using SPSS 16.1 software (RCT code: IRCT2014012113442N5). Results At the 12-month follow-up, WOMAC pain score and bodily pain significantly improved in both groups; however, better results were determined in the PRP group compared to the HA group ( P < 0.001). Other WOMAC and SF-36 parameters improved only in the PRP group. More improvement (but not statistically significant) was achieved in patients with grade 2 OA in both the groups. Conclusion This study suggests that PRP injection is more efficacious than HA injection in reducing symptoms and improving quality of life and is a therapeutic option in select patients with knee OA who have not responded to conventional treatment.

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