| Coverage Policy Manual | |
| Policy #: | 2009049 |
| Category: | Surgery |
| Initiated: | December 2009 |
| Last Review: | May 2024 |
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| Platelet-Rich Plasma (Autologous Growth Factors) | |
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| Description: |
Platelet-derived growth factors (PDGF) are frequently used as an adjunct to surgery, including but not limited to their use in periodontal, plastic/reconstructive, or orthopedic procedures; adjunctive use of PDGF is considered outside the scope of this policy. This policy only discusses use of blood-derived growth factors as a primary treatment.
A variety of growth factors have been found to play a role in wound healing, including platelet-derived growth factors (PDGF), epidermal growth factor, fibroblast growth factors, transforming growth factors, and insulin-like growth factors. Autologous platelets are a rich source of PDGF, transforming growth factors (that function as a mitogen for fibroblasts, smooth muscle cells, and osteoblasts), and vascular endothelial growth factors.
Autologous platelet concentrate suspended in plasma, also known as platelet-rich plasma (PRP), can be prepared from samples of centrifuged autologous blood. Exposure to a solution of thrombin and calcium chloride degranulates platelets, releasing the various growth factors and results in the polymerization of fibrin from fibrinogen, creating a platelet gel. The platelet gel can then be applied to wounds or may be used as an adjunct to surgery to promote hemostasis and accelerate healing. In the operating room setting, platelet-rich plasma has been investigated as an adjunct to various periodontal, reconstructive, and orthopedic procedures. For example, bone morphogenetic proteins are a type of transforming growth factors, and thus platelet-rich plasma has been used in conjunction with bone-replacement grafting (using either autologous grafts or bovine-derived xenograft) in periodontal and maxillofacial surgeries. Alternatively, platelet-rich plasma may be injected directly into various tissues. platelet-rich plasma injections have been proposed as a primary treatment of miscellaneous conditions, such as epicondylitis, plantar fasciitis, and Dupuytren contracture. Alternatively, platelet-rich plasma may be injected directly into the tissue. Injection of platelet-rich plasma for tendon and ligament pain is theoretically related to prolotherapy, the injection of chemical irritants that are intended to stimulate inflammatory responses and induce release of endogenous growth factors. Platelet-rich plasma is distinguished from fibrin glues or sealants, which have been used for many years as a surgical adjunct to promote local hemostasis at incision sites. Fibrin glue is created from platelet-poor plasma, and consists primarily of fibrinogen. Commercial fibrin glues are created from pooled homologous human donors; Tissel (Baxter) and Hemaseal are examples of commercially available fibrin sealants. Autologous fibrin sealants can be created from platelet-poor plasma. This policy does not address the use of fibrin sealants.
The U.S. Food and Drug Administration (FDA) regulates human cells and tissues intended for implantation, transplantation, or infusion through the Center for Biologics Evaluation and Research, under Code of Federal Regulation, title 21, parts 1,270 and 1,271. Blood products such as platelet-rich plasma are included in these regulations. Under these regulations, certain products including blood products such as platelet-rich plasma are exempt and therefore do not follow the traditional FDA regulatory pathway. To date, the FDA has not attempted to regulate activated platelet-rich plasma.
A number of platelet-rich plasma preparation systems are available, many of which were cleared for marketing by the FDA through the 510(k) process for producing platelet-rich preparations intended to be mixed with bone graft materials to enhance the bone grafting properties in orthopedic practices. The use of platelet-rich plasma outside of this setting (eg, an office injection) would be considered off-label. The Aurix System™ (previously called AutoloGel™; Cytomedix) and SafeBlood® (SafeBlood Technologies) are 2 related but distinct autologous blood-derived preparations that can be used at the bedside for immediate application. Both AutoloGel™ and SafeBlood® have been specifically marketed for wound healing. Other devices may be used during surgery (eg, Medtronic Electromedics, Elmd-500 Autotransfusion system, the Plasma Saver device, the SmartPRePÒ [Harvest Technologies] device). The Magellan™ Autologous Platelet Separator System (Medtronic Sofamor Danek) includes a disposable kit for use with the Magellan™ Autologous Platelet Separator portable tabletop centrifuge. GPS®II (BioMet Biologics), a gravitational platelet separation system, was cleared for marketing by the FDA through the 510(k) process for use as disposable separation tube for centrifugation and a dual cannula tip to mix the platelets and thrombin at the surgical site. Filtration or plasmapheresis may also be used to produce platelet-rich concentrates. The use of different devices and procedures can lead to variable concentrations of activated platelets and associated proteins, increasing variability between studies of clinical efficacy.
No specific CPT codes describe the preparation of autologous blood-derived products. The use of CPT code 20926 (tissue graft, other) to describe the overall procedure is not appropriate.
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Policy/ Coverage: |
Effective November 2021
Does Not Meet Primary Coverage Criteria Or Is Investigational For Contracts Without Primary Coverage Criteria
Autologous blood-derived preparations (i.e., platelet-rich plasma) for the adjunctive or primary treatment of any clinical condition, including but not limited to orthopedic conditions (e.g., epicondylitis [i.e., tennis elbow], plantar fasciitis, or Dupuytren’s contracture) or any condition not addressed in a separate policy (e.g., 1997176) does not meet primary coverage criteria of effectiveness in improving health outcomes.
For members with contracts without primary coverage criteria, the use of autologous blood-derived preparations (i.e., platelet-rich plasma) for the adjunctive or primary treatment of any clinical condition, including but not limited to orthopedic conditions (e.g., epicondylitis [i.e., tennis elbow], plantar fasciitis, or Dupuytren’s contracture) or any condition not addressed in a separate policy (e.g., 1997176) is considered investigational. Investigational procedures are an exclusion in most member benefit certificates of coverage.
Effective Prior to November 2021
Autologous blood-derived preparations (i.e., platelet-rich plasma) for the adjunctive or primary treatment of orthopedic conditions including, but not limited to, epicondylitis (i.e., tennis elbow), plantar fasciitis, or Dupuytren’s contracture, do not meet primary coverage criteria. The use of platelet rich plasma is the subject of ongoing trials. Concerns about the use of platelet rich plasma are expressed in current medical literature because of the lack of good clinical trials.
For members with contracts without primary coverage criteria, the use of autologous blood-derived preparations (i.e., platelet-rich plasma) for the adjunctive or primary treatment of orthopedic conditions is considered investigational for orthopedic conditions including, but not limited to, epicondylitis (i.e., tennis elbow), plantar fasciitis, or Dupuytren’s contracture. Investigational procedures are an exclusion in the member benefit certificate.
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| Rationale: |
One abstract was identified from a 2005 meeting presentation that described the use of percutaneous injection of PRP as a treatment of lateral epicondylitis in a prospective controlled study of 20 patients; a full report was published by Mishra and Pavelko in 2006. Criteria for participation included elbow epicondylar pain for longer than 3 months and at least 60 of 100 on a VAS with failure of conservative therapy (a standardized stretching and strengthening protocol, and some combination of non-steroidal medication, bracing, or corticosteroid injections). Twenty (15%) of the 140 patients evaluated met the inclusion/exclusion criteria. Fifteen patients were treated with PRP and 5 patients were injected only with bupivacaine with epinephrine into the skin, subcutaneous tissue and directly into the area of maximum tenderness. Either 2–3 mL PRP or 2–3 mL bupivacaine with epinephrine was injected into the common extensor or flexor tendon using a single skin portal with 5 penetrations of the tendon (peppering technique). Although drawing of 55 mL of blood in control patients (to conceal the treatment allocation) was not permitted by the institutional review board, participants were informed that the needling alone was expected to improve symptoms. All participants were given a standardized post-treatment stretching and strengthening program. At 4 weeks after the procedure, PRP-treated patients reported a mean 46% improvement (80 to 43) in VAS pain scores and a 42% improvement (50 to 71) in Mayo elbow scores. Control patients reported a mean 17% improvement (86 to 71) in VAS and 20% improvement (50 to 60) in Mayo elbow scores. The PRP-treated patients continued to improve over follow-up. At a mean of 26 months’ follow-up PRP-treated patients reported a 93% reduction in pain compared with before the procedure. Follow-up was limited in the control patients as 3 of 5 (60%) had either sought treatment outside of the protocol or had formally withdrawn from the study by 8 weeks. No complications were noted in either group at any time. Mishra and colleagues (2009) report that a double-blind prospective trial with 230 patients had been initiated in the United States using this protocol.
Nin (2009) reported results in 100 patients undergoing arthroscopic patellar tendon allograft ACL reconstruction, 50 received platelet-enriched gel (PDGF) inside the graft and tibial tunnel, 50 did not. At 2-years follow-up there was no discernable clinical or biomedical effect. There was no statistically significant difference for inflammatory parameters in the two groups.
Hall and colleagues (2009) cautioned that minimal clinical evidence is currently available yet the use of platelet-rich plasma has increased. “Many controlled clinical trials are under way, but clinical use should be approached cautiously until high-level clinical evidence supporting platelet-rich efficacy is available.”
Foster and colleagues (2009) states the use of autologous products is a rapidly growing field of orthopedics focusing on manipulating growth factors and secretory proteins to maximize healing of bone and soft tissue. “Despite their clinical use, many of these products have not been studied using rigorous scientific standards.” “Before adopting PRP into a sports medicine practice, it is important to assess the evidence in the literature that supports its safety and efficacy.” The authors state there are significant questions to be addressed:
Harnack (2009) reported 22 patients with contralateral bony defects that were randomized to beta-TCP (Cerasorb) in combination with PRP or alone. In early healing parameters and at 6 months PRP did not improve results achieved with beta-TCP in the treatment of intrabony defects.
One trial, industry sponsored, was completed in 2009 but results have not yet been published:
NCT00757289 compares PRP with corticosteroid injection for treatment of tennis elbow.
There are other ongoing trials involving PRP in total knee replacement, in rotator cuff repair, in meniscus repair, medial retinaculum tear, Achilles tendon tear, MCL tear, periodontal regeneration and bone augmentation in post-extraction sockets.
In Jan 2010 de Vos and colleagues reported a single center study of 54 randomized patients with chronic tendinopathy 2 to 7 cm above the Achilles tendon insertion. All had eccentric exercises and PRP injection (n=27) or saline injection (n-27). Pain score and activity level were completed at baseline and 6, 12, & 24 weeks utilizing the validated Victorian Institute of Sports Assessment-Achilles (VISA-A). At 24 weeks the mean VISA-A improved 21.7 points in the PRP group (95% CI,13 - 30.5) and by 20.5 points in the placebo group (95% CI, 11.6 - 29.4). There were no significant differences in secondary outcomes of patient satisfaction and return to sports activity between the two groups. (NCT00761423)
2012 Update
A search of the MEDLINE database through September 2012 did not reveal any new information that would prompt a change in the coverage statement.
A search of the clinicaltrials.gov website identified 17 clinical trials assessing the use of platelet-rich plasma for orthopedic applications. Several of these trials are listed as completed but do not have study results or publications provided. The following studies are listed as ongoing:
NCT01670578-Platelet-rich Plasma vs Viscosupplementation in the Treatment of knee Articular Degenerative Pathology . Randomized, double-blind trial of PRP vs hyaluronic acid. Single site study conducted in Italy. Estimated completion date 2013.
NCT00826098-Platelet Rich Plasma (PRP) in Total Knee Replacement. Sponsored by Exactech. Randomized, single-blind, single-center study.
NCT01238302-Arthroscopic Rotator Cuff Repair with Platelet-Rich Plasma in Large Massive Tears. Estimated study completion date October 2012. Conventional arthroscopic rotator cuff repair vs conventional repair plus PRP.
NCT01458665- Arthroscopic Rotator Cuff Repair with Platelet-Rich Plasma in Medium to Large Rotator Cuff Tears. Estimated study completion date October 2013. Conventional arthroscopic rotator cuff repair vs conventional repair plus PRP.
NCT01458691- Intra-articular Injection of Allogeneic Platelet Rich Plasma (PRP) for Adhesive Capsulitis. Randomized, Double-blind, Placebo-controlled trial. Estimated completion date December 2013.
NCT00961597- Assessment of Outcome of Meniscus Repair with or without Platelet Rich Plasma. Non-randomized, open-label trial sponsored by the Cincinnati Sportsmedicine Research and Education Foundation. Scheduled completion date December 2011.
NCT01152658- Partial Tear of Supraspinatus and Treatment with Plasma Rich in Growth Factors (PRGF). Sponsored by the Meir Medical Center. Phase 1, Randomized, double-blind trial. Estimated completion date May 2012.
2014 Update
A search of the MEDLINE database through March 2014 did not reveal any new information that would prompt a change in the coverage statement.
A search of the clinicaltrials.gov website revealed of the identified clinical trials in 2012, two have completed (NCT00826098 and NCT01238302) but no results have been published; one clinical trial (NCT01152658) was withdrawn and is no longer active. There are four ongoing clinical trials from those listed in 2012:
NCT01670578-Platelet-rich Plasma vs Viscosupplementation in the Treatment of knee Articular Degenerative Pathology . Randomized, double-blind trial of PRP vs hyaluronic acid. Single site study conducted in Italy. Estimated completion date 2013.
NCT01458665- Arthroscopic Rotator Cuff Repair with Platelet-Rich Plasma in Medium to Large Rotator Cuff Tears. Estimated study completion date October 2013. Conventional arthroscopic rotator cuff repair vs conventional repair plus PRP.
NCT01458691- Intra-articular Injection of Allogeneic Platelet Rich Plasma (PRP) for Adhesive Capsulitis. Randomized, Double-blind, Placebo-controlled trial. Estimated completion date December 2013.
NCT00961597- Assessment of Outcome of Meniscus Repair with or without Platelet Rich Plasma. Non-randomized, open-label trial sponsored by the Cincinnati Sportsmedicine Research and Education Foundation. Scheduled completion date December 2011
2016 Update
A literature search conducted through January 2016 did not reveal any new information that would prompt a change in the coverage statement.
2017 Update
A search of the MEDLINE database did not reveal any new literature that would prompt a change in the coverage statement. The following is a summary of the key identified literature.
PRP as a Primary Treatment of Tendinopathies
In 2016, Tsikopoulos et al published a systematic review that compared PRP to placebo or dry needling in patients with tendinopathy lasting at least 6 weeks (Tsikopoulos, 2016). Minimum length of follow-up was 6 months. The primary outcome of interest was pain intensity; the secondary outcome was functional disability. Five RCTs met the reviewers’ eligibility criteria. Two RCTs addressed lateral epicondylitis, 2 rotator cuff tendinopathy, and 2 patellar tendinopathy. Three studies had a saline control group and 2 compared PRP with dry needling. In a pooled analysis of all 5 trials, there was no statistically significant difference in pain intensity at 2 to 3 months with PRP or placebo/dry needling (standardized mean difference [SMD], -0.29; 95% confidence interval [CI], -0.60 to 0.02). The between-groups difference in pain intensity was statistically significant at 6 months in a pooled analysis of the 4 studies (SMD = -0.48; 95% CI, -0.86 to -0.10). The authors noted that the difference between groups in pain relief at 6 months was not clinically significant. Three studies reported functional disability levels at 3 months and a meta-analysis of these studies found significantly greater decrease in function in the PRP group (SMD = -0.47; 95% CI, -0.85 to -0.09). Functional disability 6 months postintervention was not addressed in this review.
A 2015 systematic review by Balasubramaniam et al included RCTs on PRP for tendinopathy (Balasubramaniam, 2015). In contrast to the Tsikopoulos et al (2016) review, the authors did not limit study inclusion criteria by type of control intervention or postintervention length of follow-up. The authors included 4 of the 5 RCTs in the Tsikopoulos et al review and 5 additional RCTs (total of 9). There were 4 trials on epicondylitis, 2 on rotator cuff tendinopathy, 2 on patellar tendinopathy, and 1 on Achilles tendinopathy. Comparison interventions included placebo (n=3), dry needling (n=2), autologous blood (n=2), extracorporeal shock wave therapy (n=1), and corticosteroid injections (n=2). (One study included both placebo and corticosteroid control groups.) The authors did not pool study findings due to a high level of heterogeneity among studies. In their qualitative analysis of the literature by anatomic site of tendinopathy, they concluded that 1 study on PRP for Achilles tendinopathy was insufficient to draw conclusions about efficacy. Findings of studies of other anatomic sites were mixed. Some studies showed statistically significantly greater benefit of PRP than controls on outcomes and some did not, or some studies found statistically significantly better outcomes at some time points but not others.
Knee Osteoarthritis
One placebo-controlled trial, Patel et al (2013) was identified (Patel, 2013). The RCT included 78 patients with bilateral knee osteoarthritis. Patients were randomized to receive a single injection of PRP, 2 injections of PRP, or a single saline placebo injection. There was statistically significantly greater improvement in the Western Ontario and McMaster Universities Arthritis Index (WOMAC) at 1, 3 and 6 months in the active treatment groups combined compared with the placebo group (p<0.01). The difference in WOMAC scores between patients who received 1 or 2 injections of PRP did not differ significantly.
ACL Reconstruction
A 2015 qualitative systematic review by Figueroa et al included 11 RCTs or prospective cohort studies with a combined total of 516 patients (Figueroa, 2015). Four studies found significantly faster graft maturation while 3 found no significant difference. One study showed faster tunnel healing while 5 showed no benefit. One study showed better clinical outcomes and 5 showed no improvement in clinical outcomes when using PRP.
2018 Update
A literature search conducted through January 2018 revealed no new information that would prompt a change in the coverage statement.
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through February 2019. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
PRP as a Primary Treatment for Tendinopathy
Several systematic reviews have evaluated PRP for treating mixed tendinopathies. They include trials on tendinopathies of the Achilles, rotator cuff, patella, and/or lateral epicondyle (tennis elbow). Recent (ie, 2014 to present) systematic reviews of RCTs and/or nonrandomized studies are described next. Miller et al conducted a systematic review and meta-analysis on PRP for symptomatic tendinopathy and included only RCTs with injection controls (Miller, 2017). The literature search, conducted through November 2016, identified 16 RCTs, with 18 groups (some studies included >1 tendinopathy site) for inclusion (total N=1018 patients). The Cochrane Collaboration tool was used to assess the risk of bias: 5 studies had an uncertain risk of bias, and 11 studies had a high risk of bias. The median sample size was 35 patients. Tendinopathy sites were lateral epicondylar (12 groups), rotator cuff (3 groups), Achilles (2 groups), and patellar (1 group). Preparation of PRP differed across trials as did the number of injections, with most studies administering 1injection and a few administering 2 injections. Eight of the 18 groups reported statistically significant lower pain scores using PRP compared with control and the other ten reported no differences in pain scores between trial arms. A meta-analysis reported a standard mean difference (SMD) in pain scores favoring PRP over control (0.47; 95% confidence interval [CI], 0.21 to 0.72; I2=67%).
PRP as a Primary Treatment of Knee or Hip Osteoarthritis
Xu et al acid (8 trials) or placebo (2 trials) for the treatment of knee OA (Xu 2017). Risk of bias was assessed using Cochrane criteria. Four studies were assessed as having low quality, 3 as moderate quality, and 3 as high quality. Meta-analyses including 7 of the trials comparing PRP with hyaluronic acid showed that PRP significantly improved Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) or International Knee Documentation Committee (IKDC) scores compared with HA at 6-month follow-up; however, when meta-analyses included only the 2 high-quality RCTs, there was not a significant difference between PRP and hyaluronic acid. (Note that WOMAC evaluates 3 domains: pain, scored from 0-20; stiffness, scored from 0-8; and physical function, scored from 0-68. Higher scores represent greater pain and stiffness as well as worsened physical capability. The IKDC is a patient-reported, knee-specific outcome measure that measures pain and functional activity.) In the meta-analysis comparing PRP with placebo, a third trial was included, which had four treatment groups, two of which were PRP and placebo. This analysis showed that PRP significantly improved WOMAC or IKDC scores compared with placebo; however, only one of the trials was considered high quality and that trial only enrolled 30 patients. All meta-analyses showed high heterogeneity among trials (I2≥90%).
Long Bone Nonunion
The trial study by Dallari et al, which was included in the Cochrane review, compared PRP plus allogenic bone graft with allogenic bone graft alone in patients undergoing corrective osteotomy for medial compartment osteoarthrosis of the knee (Dallari, 2007). According to Cochrane reviewers, the risk of bias in this study was substantial. Results showed no significant differences in patient-reported or clinician-assessed functional outcome scores between groups at 1 year. However, the proportion of bones united at 1 year was statistically significantly higher in the PRP plus allogenic bone graft arm (8/9) compared with the allogenic bone graft alone arm (3/9; relative risk, 2.67; 95% CI, 1.03 to 6.91). This benefit, however, was not statistically significant when assuming poor outcomes for participants who were lost to follow-up (8/11 vs 3/10; relative risk, 2.42; 95% CI, 0.88 to 6.68).
Samuel et al conducted a controlled trial in which patients with delayed unions (15-30 weeks old) were randomized to 2 PRP injections at the fracture site at baseline and 3 weeks (n=23) or no treatment (n=17) (Samuel, 2017).https://www.evidencepositioningsystem.com/_w_1985646703e69442087b4411f05a9ef225be82b4b8f87d49/ The delayed unions were in the tibia (n=29), femur (n=8), forearm (n=2), and the humerus (n=1). The main outcome was long bone union, defined as no pain or tenderness on weight bearing, no abnormal mobility, and bridging at three or more cortices in x-ray. Examinations were conducted every 6 weeks for 36 weeks or until union. Percent union did not differ significantly between the 2 groups (78% in the PRP group vs 59% in the control group). Time to union also did not differ significantly (15.3 weeks for the PRP group vs13.1 weeks for the control group).
Rotator Cuff Repair
Chen et al conducted a systematic review and meta-analysis on the efficacy of PFP for tendon and ligament healing (Chen, 2017). The literature search, conducted through April 2017, identified 37 articles for qualitative synthesis, 21 of which reported VAS outcomes and were used in a meta-analysis. Of the 21 studies, 8 enrolled patients undergoing rotator cuff repair. Patients in the PRP group experienced significant reductions in VAS pain compared with the control group at both short-term (6 months) follow-up (-0.5; 95% CI, -0.7 to -0.1) and long-term (≥1 year) follow-up (-0.5; 95% CI, -1.0 to -0.1). While findings were encouraging, reviewers warned that there was extensive variability in both the way PRP was prepared and how the PRP injections were administered.
Ebert et al (2017) published an RCT after the systematic reviews discussed above comparing rotator cuff repair alone with rotator cuff repair plus PRP treatment (Ebert, 2017). Patients were randomized to 2 ultrasound-guided injections of PRP to the tendon repair site at 7 and 14 days after arthroscopic supraspinatus repair (n=27) or not (n=28). Outcomes of interest included Oxford Shoulder Score, Quick Disabilities of the Arm, Shoulder and Hand questionnaire, and VAS score for pain. At a mean follow-up of 3.5 years, there were no statistically significant differences in any of the outcomes of interest. There was also no difference in re-tear rates, with 2 patients in each trial group experiencing symptomatic re-tears.
Practice Guidelines and Position Statements
American Academy of Orthopaedic Surgeons
AAOS issued evidence-based guidelines on the management of OA of the hip (AAOS, 2017). In the section on intra-articular injectables, the guidelines stated that there is strong evidence supporting the use of intra-articular corticosteroids to improve function and reduce pain in the short term for patients with OA of the hip. There was also strong evidence that the use of intra-articular hyaluronic acid does not perform better than placebo in improving function, stiffness, and pain in patients with hip OA. The guidelines also noted that there were no high-quality studies comparing PRP with placebo for the treatment of OA of the hip.
2020 Update
Annual policy review completed with a literature search using the MEDLINE database through December 2019. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Walsh et al published a prospective, randomized, single-blinded study evaluating PRP in fibrin matrix as a means to augment rotator cuff repair (Walsh, 2018). Seventy-six patients were randomized to either the PRP (n=32) or control group (n=44) between 2011 and 2013. At 24 months, Western Ontario Rotator Cuff scores had changed from 1106 to 94 for PRP and from 1257 to 139 for control. Rate of re-tear at 6 months was 7.4% for the PRP group and 19% for control. Strength of supraspinatus and infraspinatus were 96.6% and 103%, respectively, for PRP and 99.8% and 104%, respectively, for control. No results reached statistical significance. The study was limited by the following: (1) the study was single- rather than double-blinded, (2) no attempt was made to quantify the concentration of platelets used in the repairs, (3) follow-up was relatively short (two years), and (4) magnetic resonance imaging scans were only made at six-month follow-up.
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Johal et al conducted a systematic review and meta-analysis of RCTs on platelet-rich plasma for various orthopedic indications, including 10 RCTs of lateral epicondylitis (Johal, 2019). The meta-analysis evaluated the standardized mean difference in pain at both 3 and 12 months. Systematic review authors used the Cochrane Collaboration risk of bias tool to assess study quality. At 12 months, pain scores were statistically significantly lower for platelet-rich plasma versus its comparators (i.e., steroids, whole blood, dry needling, local anesthetics). However, these results should be interpreted with caution due to important limitations including high statistical heterogeneity (I2=73%), lack of a clinically significant difference (i.e., < effect size threshold of 0.5 for a clinically important difference), and moderate to high risk of bias in study conduct.
Four small RCTs (N=297, range of 57 to 80) have been published subsequent to the above-described systematic reviews (Gupta, 2019; Scott, 2019; Fitzpatrick, 2019; Martin, 2019). Tendinopathy sites were lateral epicondylar (2 RCT's), patellar (1 RCT), and gluteal (1 RCT). Follow-up durations ranged from 6 months to 1 year. Platelet-rich plasma protocols varied across studies including a single 3mL injection using a peppering technique, or ultrasound guided injections ranging from 3.5 mL to 6-7 mL, Concurrent rehabilitation protocols also differed, ranging from 6 weeks of supervised rehabilitation to 12 weeks of unsupervised rehabilitation. Compared to a corticosteroid injection, 2 RCTs found platelet-rich plasma injection to result in significantly improved pain scores. However, important relevancy gaps and study conduct limitations exist that preclude reaching strong conclusions based on this evidence. Additionally, compared to placebo, platelet-rich plasma did not significantly improve pain after 12 months. Finally, in the RCT by Martin et al, compared with lidocaine, in individuals receiving platelet-rich plasma as an adjunct to ultrasound-guided tenotomy for recalcitrant elbow tendinopathy there were no significant differences in the primary outcome of rate of patients with an improvement exceeding 25% in disability based on Disabilities of the Arm, Shoulder and Hand scores (DASH-E, Spanish version), or other pain outcomes.
Subsequent to the systematic review by Franceschi et al, 3 additional randomized controlled trials have been published (Peerbooms, 2019; Shetty, 2019; Johnson-Lynn, 2019). None were large double-blind RCT's of sufficient duration (i.e., 2 years) to conclusively demonstrate efficacy. The RCT's compared platelet-rich plasma treatment (total N=107) with corticosteroid injection (N=82) or saline injection (N=44). The platelet-rich plasma protocols differed across RCTs. The RCTs were small, ranging in size from 28 to 155 participants (Johnson-Lynn, 2019; Peerbooms, 2019). Follow-up duration ranged from 6 months to 18 months (Johnson-Lynn, 2019; Shetty, 2019). Two were conducted in single centers in either the UK or India and the third was a multicenter RCT of 5 sites in the Netherlands (Johnson-Lynn, 2019; Shetty, 2019). None prespecified any methods to assess potential harms. Results were mixed across RCTs. The largest RCT (n=115) by Peerbooms et al (2019) compared platelet-rich plasma with corticosteroid injection and had a follow-up to 12 months (Peerbooms, 2019). In the RCT by Peerbooms et al, the proportion of patients with at least a 25% improvement in Foot Function Index Pain Scores between baseline and 12 months was significantly greater in the platelet-rich plasma group (88.4% versus 55.6%; P=0.003). Additionally, mean Foot Function Index Disability Scores were significantly lower in the platelet-rich plasma group at 12 months (mean difference, 12.0; 95% CI, 2.3-21.6). But, these improvements did not translate into significantly greater quality of life in the platelet-rich plasma group. Also, important study design and conduct gaps exist that seriously limit the interpretation of these findings, including that analysis excluded 29% of the randomized patients, which was less than the calculated sample size. Therefore, although evidence continues to develop, important uncertainties in efficacy and safety remain and larger double-blind RCT's are still needed.
A number of RCTs and several systematic reviews of RCTs evaluating the use of platelet-rich plasma for knee osteoarthritis have been published (Johal, 2019; Laudy, 2015; Chang, 2014; Meheux, 2016; Lai, 2015; Cole, 2017; Duymus, 2017; Kanchanatawan, 2016). Protocols used in platelet-rich plasma interventions for knee osteoarthritis varied widely. For example, in the studies identified in the Laudy et al systematic review, platelet-rich plasma was prepared using single, double, or triple spinning techniques and interventions included between 1 and 3 injections delivered 1 to 3 weeks apart (Laudy, 2015).
In individuals with knee or hip osteoarthritis undergoing platelet-rich plasma injections, findings from 4 systematic reviews are reported (Johal, 2019; Xu, 2017; Laudy, 2015; Chang, 2014). The systematic reviews have varied in their outcomes of interest and their findings. Systematic reviews have generally found that platelet-rich plasma was more effective than placebo or hyaluronic acid in reducing pain and improving function. However, systematic review authors have noted that their findings should be interpreted with caution due to important limitations including significant residual statistical heterogeneity, questionable clinical significance, and high risk of bias in study conduct.
Johal et al conducted a systematic review and meta-analysis of RCTs comparing platelet-rich plasma with hyaluronic acid (8 trials, N=927), or placebo (2 trials, N=105), or no platelet-rich plasma (2 trials, N=123) or acetaminophen (1 trial, N=75), or a corticosteroid (1 trial, N=48) (Johal, 2019). Meta-analysis showed that platelet-rich plasma was more effective than its comparators at 12 months (standard mean difference, –0.91; 95% CI, –1.41 to –0.41). However, the systematic review authors noted that important limitations of this finding included lack of a clinically significant difference (i.e., less than the effect size threshold of 0.5 for a clinically important difference), high residual statistical heterogeneity between studies (I2=89%) and high risk of bias in study conduct.
In individuals with knee osteoarthritis undergoing platelet-rich plasma injections, 3 RCTs with follow-up durations of at least 12 months have been published subsequent to the above-described systematic reviews (Huang, 2019; Di Martino, 2019; Lin, 2019). All were conducted outside of the United States. Sample sizes ranged from 87 to 192 participants. Comparator treatments included hyaluronic acid in all 3 RCTs, and corticosteroids or placebo in 2 RCTs. Two of the RCTs found statistically significantly greater 12-month reductions in the Western Ontario and McMaster Universities Osteoarthritis Index scores with platelet-rich plasma versus the comparator treatments (Huang, 2019; Lin, 2019). However, these findings should be interpreted with caution due to important study conduct limitations, including potential inadequate control for selection bias and unclear blinding. Additionally, no significant differences between platelet-rich plasma and hyaluronic acid were found in the International Knee Documentation Committee (IKDC) subjective score or EuroQol visual analog scale score in the longest-term trial with 5 years of follow-up (Di Martino, 2019). In the RCT by Di Martino et al (2019) reintervention rates were significantly lower with platelet-rich plasma compared with hyaluronic acid at the 24-month follow-up assessment (22.6% 37.1%; P=0.036), but the difference was not maintained at 5 years.
The literature on platelet-rich plasma for rotator cuff repair consists of several RCTs and systematic reviews that have evaluated the efficacy of platelet-rich plasma membrane or matrix combined with surgical repair of the rotator cuff. The systematic reviews have varied in their outcomes of interest and findings (Wang, 2019; Johal, 2019; Moraes, 2013; Zhao, 2015; Yang, 2016; Cai, 2015). For pain outcomes, systematic reviews consistently found significant reductions with platelet-rich plasma at 12 months (Chen, 2017; Wang, 2019; Johal, 2019). However, systematic review authors noted that the pain findings should be interpreted with caution due to significant residual statistical heterogeneity, lack of a clinically significant difference (i.e., less than the effect size threshold of 0.5 for a clinically important difference), and high risk of bias in study conduct. Additionally, the 12-month pain reduction with platelet-rich plasma was not maintained in RCTs with longer-term follow-up of 24 months or longer (Chen, 2017; Wang, 2019; Johal, 2019). Systematic reviews generally did not show a statistically or clinically significant benefit of platelet-rich plasma on other outcomes, including function, retear rate and Constant scores. No reviews have demonstrated a consistent statistical and clinical significant benefit of platelet-rich plasma across multiple outcomes of interest for the 3.5 years of follow-up that is considered necessary to conclusively demonstrate efficacy. The systematic review by Wang et al reported on adverse effects. Wang et al reported that complications were only reported in 1 of the included RCTs, occurring in 5.6% of participants in the platelet-rich plasma groups and none in the control groups (Wang, 2019). The complications included infection, hematoma, and an exanthematous itchy skin lesion in 1 patient each.
Three small, single-center RCTs have been published subsequent to the systematic reviews described above (Walsh, 2018; Malavolta, 2018; Snow, 2019). Walsh et al published a prospective, randomized, single-blinded study evaluating platelet-rich plasma in fibrin matrix as a means to augment rotator cuff repair (Walsh, 2018). Malavolta et al published 5-year clinical and structural evaluations in follow-up to their 2014 publication of their 24-month results (Malavolta, 2018). In contrast to previous RCT’s that have focused on administration of platelet-rich plasma at the time of rotator cuff repair surgery, the third RCT, published by Snow et al, was unique in publishing a randomized double-blind trial of delayed delivery of platelet-rich plasma at 10-15 days post-surgery (Snow, 2019). Sample sizes ranged from 51 patients to 97 patients (Malavolta, 2018; Snow, 2019). Results of these 3 RCTs are consistent with the systematic reviews in finding no statistically or clinically significant benefit of platelet-rich plasma on multiple outcomes.
One small (N=62), unblinded, single-center RCT for spinal fusion conducted in Japan and published by Kubota et al was identified that compared platelet-rich plasma to no platelet-rich plasma (Kubota, 2019). Follow-up was 24 months. Although fusion rates were significantly improved with platelet-rich plasma, there were no significant differences in visual analog scale scores between the 2 groups. Major limitations of this RCT include that patients were unblinded to treatment and there was no placebo comparator.
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
An additional RCT has been published comparing platelet-rich plasma treatment with corticosteroid injection or saline injection (Tabrizi, 2020). Like the others, this was not a large double-blind RCT of sufficient duration (i.e., 2 years) to conclusively demonstrate efficacy. The RCT took place in a single center in Iran with follow-up duration of 6 months. There we no prespecified methods to assess potential harm. Uncertainties in efficacy and safety remain and larger double-blind RCTs are still needed.
In individuals with knee osteoarthritis undergoing platelet-rich plasma injections, findings from 5 systematic reviews are reported (Trams, 2020; Johal, 2019; Xu, 2017; Laudy, 2015; Chang, 2014). The systematic reviews have varied in their outcomes of interest and their findings. Systematic reviews have generally found that platelet-rich plasma was more effective than placebo or hyaluronic acid in reducing pain and improving function. However, systematic review authors have noted that their findings should be interpreted with caution due to important limitations including significant residual statistical heterogeneity, questionable clinical significance, and high risk of bias in study conduct.
Trams et al published a systematic review that included 38 RCTs (N=2962) evaluating the effects of platelet-rich plasma on patients with knee osteoarthritis (Trams, 2020). The meta-analysis focused on the review of 33 blinded studies. Follow-up ranged from 6 months to 2 years. Comparators included hyaluronic acid in 23 studies, placebo (eg, saline, no injection, physical therapy) in 10 studies, corticosteroids in 4 studies, and acetaminophen in 2 studies. Twenty-two studies reported VAS pain outcomes for placebo (n=5), hyaluronic acid (n=15), and corticosteroids (n=2). Placebo and hyaluronic acid subgroups showed significant VAS differences in favor of platelet-rich plasma (p<0.00001). The corticosteroid subgroup was not significantly different from platelet-rich plasma (p=0.23). Six studies comparing single versus multiple injections of platelet-rich plasma showed a significant difference in favor of 3 platelet-rich plasma injections (p<0.00001). Functional outcomes were reported via the Western Ontario and McMaster Osteoarthritis Index (WOMAC) scale for placebo (n=9), corticosteroids (n=1), and hyaluronic acid (n=15). Both pooled and subgroup analyses favored platelet-rich plasma (p<0.00001). In 5 studies assessing multiple versus single platelet-rich plasma injections, significant differences in favor of multiple injections were found (p<0.00001). Functional outcomes assessed via International Knee Documentation Committee (IKDC) scores were reported in 2 placebo studies and 5 hyaluronic acid studies. While a significant difference was found for hyaluronic acid (p=0.004), no significant difference was found for placebo (p=0.24). Pooled estimates for 6 studies comparing platelet-rich plasma to corticosteroids, hyaluronic acid, or mesenchymal stem cells found no significant differences in Knee injury and Osteoarthritis Outcome Score (KOOS) sport, quality of life, activities of daily living, symptoms, or pain subscales. The pooled estimates for adverse events showed non-significant differences in favor of the control groups (p=0.15). Risk of bias was assessed using Cochrane criteria. One study was at high risk of bias for 3 domains, 2 studies were at high risk of bias for 2 domains, and 12 studies were at high risk of bias for 1 domain. The most impacted domains were performance bias and reporting bias.
In individuals with knee osteoarthritis undergoing platelet-rich plasma injections, 2 RCTs with follow-up durations of at least 12 months have been published subsequent to the above-described systematic reviews (Reyes-Sosa, 2020; Elksnins-Finogejevs, 2020). All trials were conducted outside of the United States. Sample sizes ranged from 40 to 60 patients. Comparator treatments included corticosteroids or celecoxib. Both RCTs found statistically significantly greater 1-year reductions in pain and function scores with platelet-rich plasma versus the comparator treatments. However, these findings should be interpreted with caution due to important study conduct limitations, including potential inadequate control for selection bias and limited or unclear blinding. No significant differences in pain or function scores were observed within the first month of treatment in either study
A systematic review and meta-analysis by Trams et al identified 16 RCTs (total N=740 patients) (Trams, 2020). Five studies showed no significant overall difference with respect to pain (p=0.43). In 4 studies reporting IKDC scores, no significant differences were noted (p=0.83). In 4 studies, no significant differences in functional outcomes as measured by the Lysholm score were reported (p=0.19). Pooled estimates for Tegner scale activity assessments in 5 studies showed no significant differences (p=0.38) in favor of the control. Twelve studies were deemed to be at high risk of bias in at least 1 domain.
The literature on platelet-rich plasma for rotator cuff repair consists of several RCTs and systematic reviews that have evaluated the efficacy of platelet-rich plasma membrane or matrix combined with surgical repair of the rotator cuff., The systematic review by Chen et al did not show a statistically or clinically significant benefit of platelet-rich plasma on the following outcomes: function, retear rate and Constant scores (Chen, 2020).
Trams et al published a systematic review and meta-analysis that included 6 RCTs (N=621) evaluating the effects of intraoperative platelet-rich plasma as an adjunct to total knee arthroplasty (Trams, 2020). Two studies were deemed at high risk of bias. The primary aim of the studies was to assess blood loss during the procedure. While there were significant differences in favor of platelet-rich plasma in the overall effect on blood parameters in comparison to the control groups (standard mean difference, -0.29; 95% CI, -0.46 to -0.11), no significant differences in range of motion, functional outcomes, or long-term pain were observed.
2023 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2023. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
Dai et al conducted a systematic review and meta-analysis of RCTs evaluating platelet-rich plasma versus control (saline injection, dry needling, or no treatment) for the treatment of tendinopathy (Dai, 2021). A total of 13 trials met the eligibility criteria and included patients with lateral epicondylitis (5 RCTs), Achilles tendinopathy (4 RCTs), rotator cuff tendinopathy (2 RCTs), and patellar tendinopathy (2 RCTs). Among the 13 RCTs, 7 studies were judged to be at low risk of bias and 6 were found to have a high risk of bias. The meta-analysis demonstrated that platelet-rich plasma was not superior to control for the primary outcomes of change in pain intensity or function at 12 weeks; these trends also persisted at 24 weeks. The authors noted that included trials displayed significant heterogeneity with respect to platelet-rich plasma preparation and patient characteristics, and had important methodological limitations.
Muthu et al conducted a systematic review with meta-analysis of RCTs comparing platelet-rich plasma, autologous blood, corticosteroids, local anesthetics, laser therapy, and surgery for patients with lateral epicondylitis (Muthu, 2022). A total of 25 trials met the eligibility criteria (N=2040). Results demonstrated that based on data from 22 trials, only leukocyte-rich platelet-rich plasma significantly improved visual analog scale (VAS) pain scores compared to saline control (weighted mean difference [MD], -14.8; 95% confidence interval [CI], -23.18 to -6.39); in a subgroup analysis of 14 studies with at least 12 months of follow up, the weighted MD did not reach statistical significance (-7.69; 95% CI, -27.28 to 11.90). Based on data from 11 trials, none of the interventions were superior to saline control for improvement in the Disabilities of the Arm, Shoulder, and Hand (DASH) score. Treatment ranking based on the P-score approach demonstrated that leukocyte-rich platelet-rich plasma was most likely to be the best treatment amongst autologous blood, corticosteroids, laser therapy, local anesthetics, and leukocyte-poor platelet-rich plasma.
One larger RCT was also published in 2021 (N=240) (Kearney, 2021). Tendinopathy sites were lateral Achilles (1 RCT), epicondylar (2 RCTs), patellar (1 RCT), and gluteal (1 RCT). Follow-up ranged from 6 months to 2 years. Platelet-rich plasma protocols varied across studies including a single 3 mL injection using a peppering technique, or ultrasound-guided injections ranging from 3.5 mL to 6 to 7 mL. Concurrent rehabilitation protocols also differed, ranging from 6 weeks of supervised rehabilitation to 12 weeks of unsupervised rehabilitation. Compared to a corticosteroid injection, 2 RCTs found platelet-rich plasma injection to result in significantly improved pain scores. However, important relevancy gaps and study conduct limitations exist that preclude reaching strong conclusions based on this evidence. Additionally, compared to placebo, platelet-rich plasma did not significantly improve pain after 6 or 12 months.
Anil et al published a systematic review with network meta-analysis to compare the efficacy of nonoperative injectable treatments for knee osteoarthritis (Anil, 2021). A total of 79 RCTs (N=8761) were included and the follow-up ranged from 4 weeks to 24 months. Intra-articular injectable treatments included platelet-rich plasma, autologous conditioned serum, bone marrow aspirate concentrate, botulinum toxin, corticosteroids, hyaluronic acid, mesenchymal stem cells, ozone, saline placebo, plasma rich in growth factor, and stromal vascular fraction; the publication did not delineate the number of RCTs that specifically evaluated on platelet-rich plasma. At 12 months, the treatment with the highest P-Score for the MD in Western Ontario and McMaster Osteoarthritis Index (WOMAC) scale score and VAS score was stromal vascular fraction. However, the MD in WOMAC scale and VAS scores for leukocyte-poor platelet-rich plasma and leukocyte-rich platelet-rich plasma versus saline placebo at 12 months did not reach statistical significance.
In individuals with hip osteoarthritis undergoing platelet-rich plasma injections, findings from 2 systematic reviews are reported. The study by Belk et al identified 6 RCTs comparing the efficacy of platelet-rich plasma (n=211) and hyaluronic acid injections (n=197) (Belk, 2021). The mean follow-up was approximately 12 months. In an analysis of 4 RCTs, platelet-rich plasma and hyaluronic acid groups had similar improvements in VAS score (MD, 5.9; 95% CI, -0.741 to 1.92) and WOMAC score (MD, 0.27; 95% CI, -0.05 to 0.59).
Sdeek et al reported on the results of a 36-month RCT that compared 3 intraarticular injections of either platelet-rich plasma (n=95) or hyaluronic acid (n=94) in patients with knee osteoarthritis (Sdeek, 2021). Both platelet-rich plasma and hyaluronic acid were effective in improving pain and functional status. Statistical analyses were not performed, however, trends for pain and function scores showed greater improvement in the group that received platelet-rich plasma. The findings of these RCTs should be interpreted with caution due to important study conduct limitations, including potential inadequate control for selection bias and limited or unclear blinding. No significant differences in pain or function scores were observed within the first month of treatment in either study.
Bailey et al reported on a retrospective matched case-control study evaluating the effects of intraoperative platelet-rich plasma on postoperative knee function and complications at 2 years after ACL reconstruction with meniscal repair (Bailey, 2021). The study was conducted between 2013 and 2017 and included 162 patients who received platelet-rich plasma and 162 patients who did not. Results demonstrated that there were no differences in knee function scores between the platelet-rich plasma and matched-control groups at 2 years, as well as no differences in the timing of return to activity (mean, 7.8 vs 8.0 months; p=.765). However, the platelet-rich plasma group demonstrated a higher rate of postoperative knee motion loss compared with the control group (13.6% vs 4.6%; p<.001).
The literature on platelet-rich plasma for rotator cuff repair consists of several RCTs and systematic reviews that have evaluated the efficacy of platelet-rich plasma membrane or matrix combined with surgical repair of the rotator cuff. One systematic review found a statistically significant reduction in retear rate in a subgroup analysis of 4 long-term RCTs that were at least 24 months in duration (Li, 2022).
Randelli et al published results of a 10-year follow-up of the 2011 double-blind RCT by Rangelli et al that included 53 patients randomized to receive arthroscopic rotator cuff repair with or without the addition of platelet-rich plasma. Randelli et al included data for 17 patients who received platelet-rich plasma and 21 control group patients (Randelli, 2021). At the 10-year follow-up, both platelet-rich plasma and control groups experienced improvements in the median (interquartile range [IQR]) University of California at Los Angeles activity score (34 [29 to 35] and 33 [29 to 35] points, respectively) and VAS score (0.34 [0 to 1.85] and 0.70 [0 to 2.45] points, respectively); the between-group differences did not reach statistical significance. Furthermore, approximately 37% of the operated patients had a re-rupture in each group. Retears occurred in 6% of the patients who received platelet-rich plasma treatment and 14% of patients in the control group (p=.61).
In 2021, the American Academy of Orthopaedic Surgeons (AAOS) guidelines for the management of osteoarthritis of the knee made the following recommendation (AAOS, 2021):
"Platelet-rich plasma (PRP) may reduce pain and improve function in patients with symptomatic osteoarthritis of the knee. (Strength of Recommendation: Limited)" The variability of study findings was noted to have contributed to the low strength of recommendation rating.
2024 Update
Annual policy review completed with a literature search using the MEDLINE database through January 2024. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
A systematic review and meta-analysis identified 17 RCTs (N=970) in patients undergoing ACL reconstruction (Lv, 2022). Compared to controls, platelet-rich plasma improved VAS score (MD, -1.12; 95% CI, -1.92 to -0.31; p=.007),Lysholm score (MD, 8.49; 95%CI, 1.63 to 15.36) and subjective IKDC score (MD, 6.08; 95% CI, 4.39 to 7.77; p<.00001) at 6months. The authors only considered the difference in pain score to be clinically relevant, and they did not consider any differences between groups at 12 months to be clinically meaningful (VAS MD, -0.47 and subjective IKDC score MD, 3.99).Overall, the evidence was determined to be of moderate quality.
A systematic review and meta-analysis was conducted of 33 RCTs (N=2025) comparing ultrasound-guided platelet-rich plasma to control (injection of steroids, saline, autologous whole blood, mesenchymal stem cells, or local anesthetic; dry needling; prolotherapy; or other non-injection intervention) for the treatment of tendinopathy (Masiello, 2022). Tendinopathies included lateral epicondylitis (n=8), plantar fasciitis (n=5), Achilles tendinopathy (n=5), rotator cuff tendinopathy (n=7), patellar tendinopathy(n=3), and carpal tunnel syndrome (n=3). Most trials (n=20) administered platelet-rich plasma as a single injection; however, up to 4 injections were administered in some trials. Few differences in efficacy between control and platelet-rich plasma were found with the exception of patients with carpal tunnel where pain and severity scores were reduced in the short and medium term. Results were reported for individual tendinopathies and, therefore, are not included in Table 2. However, overall mean differences in pain scores were: -0.24 (95% confidence interval [CI], -0.73 to 0.25) for lateral epicondylitis, -3.62 (95% CI, -8.16 to0.91) for plantar fasciitis, -0.17 (95% CI, -4.25 to 3.90) for Achilles tendinopathy, 0.16 (95% CI, -0.18 to 0.50) for rotator cuff tendinopathy, 0.17 (95% CI, -0.64 to 0.98) for patellar tendinopathy, and -0.24 (95% CI, -0.32 to -0.16) for carpal tunnel syndrome. The evidence was rated as low quality due to risk of bias, imprecision, and inconsistency.
A RCT was conducted comparing platelet-rich plasma with hyaluronic acid in patients with hip osteoarthritis (Nouri, 2022). A total of 105 patients were randomized to platelet-rich plasma, hyaluronic acid, or the combination. There were no differences in VAS scores between groups at 6 months; however, functional outcomes were improved in the platelet-rich plasma groups compared with hyaluronic acid alone.
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