Validation of a Low-cost Platelet-Rich Plasma (PRP)

Study Overview
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Brief Summary
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Knee osteoarthritis is an extremely common and debilitating condition, more common in women, with an estimated global prevalence of 16%, and as high as 50% by the age of 80. Current management of knee osteoarthritis (OA) revolves around conservative treatments- biomechanical interventions, intra-articular injections, exercise, self-management and education, oral or topical medications, strength training, and weight management - or surgical management. For injection therapies, corticosteroids remain the standard of care; approximately 84% of sports medicine physicians perform these knee injections at least monthly, reporting a median range of 11-20 injections per month. Multiple detrimental effects of corticosteroid injections are well-known, including alterations of the hypothalamic-pituitary-adrenal axis, blood glucose levels, bone turnover, inflammatory response, blood pressure, and psychologic well-being. Thus, alternative therapies are of the utmost importance. Platelet-Rich Plasma (PRP) is an injectable preparation of a patient's blood that can be used for numerous conditions and has received significant attention over the past several years for its potential application for the treatment of pain and functional impairment due to knee OA. Systematic reviews of randomized-controlled trials have demonstrated equivalent-to-superior treatment outcomes associated with the use of intra-articular PRP compared to placebo, hyaluronic acid, and corticosteroid. Furthermore, use of intra-articular PRP is associated with a very low rate of adverse events and is likely safer than injectable corticosteroids. Concerns that have limited a wider use of PRP include two main concerns - an uncertainty regarding the current evidence base due to study-related bias, heterogeneity, and lack of reporting standards; and second, more importantly, the main issue remains high cost.

Detailed Description
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Study Purposes and Objectives: The study will directly address two concerns - proper reporting of PRP composition and greatly decreasing cost. As socioeconomic inequity directly relates to disability related to knee Osteoarthritis (OA), limiting the cost of treatment is of the utmost importance to ensure appropriate delivery of care to all patients. As PRP is currently not covered by the vast majority of public and private payors, patients are required to pay for the injections out of pocket, with an average cost of $714 per injection (as high as $2,092). Furthermore, research studies relating to PRP are often expensive due to the cost of the traditional method of extracting PRP, generally with commercial kits, and thus limited in scope. The investigators have developed and implemented a low-cost PRP (LC-PRP) preparation technique and have safely performed the injections on hundreds of patients with knee OA. The cost of this preparation technique is equivalent to the cost of a vial of corticosteroid and it is easy to replicate. In conjunction with Internal Departmental matching funds, this grant will cover the cost of resources to support the study, which will allow for future clinical and research endeavors in this realm. The primary goal of this study is to validate this easy-to-replicate LC-PRP preparation technique to demonstrate that its composition is equivalent to standard, commercially-available PRP preparation kits. Validation must include data that match the minimum reporting standards for clinical studies evaluating PRP. Once validated, this will allow for a low-cost method to prepare PRP in countless clinical and research realms. Specifically, the investigators will analyze the components of both the whole blood (the subject's blood from which the PRP is extracted) and the PRP itself. Based on extensive pilot data, the platelet yield - the amount of platelets extracted from the patient's whole blood - is equivalent to those seen from expensive, commercially-available kits. Though this study will use neutrophil-poor PRP, this method can just as easily create neutrophil-rich PRP for other future clinical needs. The investigators secondary goal is to prospectively evaluate pain and functional outcomes in a cohort of patients with knee OA. Based on the investigators pilot data, zero significant adverse events have been reported after treatment of over 1,000 patients with this technique in two separate geographical regions. The investigators have incomplete clinical outcome data, but it preliminarily demonstrates positive outcomes at 3 and 6 months in cohort. The investigators plan on using the results of this validation study to seek external funding for a randomized-controlled trial (RCT) comparing LC-PRP to corticosteroid injection for knee OA. The investigator's tertiary goal is to conduct a cost-effectiveness analysis of LC-PRP compared to corticosteroid injection from a payor perspective using a computer simulation model. This simulation model, to be performed by Dr. Nelson, will be parameterized using a combination of data from the proposed study and from previously published literature. This model will also be a stepping stone for a cost-effectiveness analysis that will be conducted alongside the aforementioned future RCT.

Official Title
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Validation of a Low-cost Platelet-Rich Plasma (PRP)

Conditions
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Platelet-Rich Plasma (PRP), Knee Osteoarthritis (OA)

Intervention / Treatment
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* Procedure: Intra-Articular knee injection of LC-PRP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of any adult age with symptomatic Kellgren-Lawrence (K-L) score 1-3 knee OA, based on radiographs within the last six months. Patients must have failed at least six weeks of conventional conservative treatments (such as medication or physical therapy). Patients with bilateral knee OA will only be eligible if both knees fit the criteria; each knee will count separately. Exclusion Criteria: Recent (last two years) knee surgery, Prior orthobiologic injection(s) into the knee, Known major axial deviation (over 30 degrees) Known thrombocytopenia (platelets under 50,000), thrombocythemia (platelets over 1,000,000), known platelet disorder (ITP, TTP, or Lowe syndrome) Active systemic infection requiring antibiotics, or local infection at the site of injection, Non-ambulatory patients, Patients seeking care with active litigation pending Body mass index (BMI) over 40 Injection into the affected joint within the last six months Oral steroids consumed within the last three months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Recruitment will take place at the University of Utah Orthopedic Center by physician and study study staff members EMR chart review prior to patient visits. The investigator plans to recruit a total of 30 participants to this project over a 24 month period of time.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Directly Address Two Concerns - Proper Reporting of PRP Composition and Greatly Decreasing Cost<br>As socioeconomic inequity directly relates to disability related to knee Osteoarthritis (OA), limiting the cost of treatment is of the utmost importance to ensure appropriate delivery of care to all patients. As PRP is currently not covered by the vast majority of public and private payors, patients are required to pay for the injections out of pocket, with an average cost of $714 per injection (as high as $2,092). Furthermore, research studies relating to PRP are often expensive due to the cost of the traditional method of extracting PRP, generally with commercial kits, and thus limited in scope. The investigators have developed and implemented a low-cost PRP (LC-PRP) preparation technique and have safely performed the injections on hundreds of patients with knee OA. | Procedure: Intra-Articular knee injection of LC-PRP<br>* Blood Collection 45mL, Processed Neutrophil-Poor PRP, 2 Injections at day 0 and 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary goal of this study is to validate our easy-to replicate LC-PRP preparation technique | The primary goal of this study is to validate the investigator(s) easy-to-replicate LC-PRP preparation technique to demonstrate that its composition is equivalent to standard, commercially-available PRP preparation kits. The investigators will specifically compare the quantity of platelets derived from their system compared to previously published platelet counts for commercially available PRP preparation kits. | 24-Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain and functional outcomes | Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at 1, 3, 6, and 12 months after the second injection. Lastly, the investigator(s) will be evaluating adverse events for safety purposes.(functional and pain measure) | 24-Months | 
| QOL outcomes | EQ-5D (EuroQual, quality of life measure) at 1, 3, 6, and 12 months after the second injection. Lastly, the investigator(s) will be evaluating adverse events for safety purposes. | 24-Months | 
| Global impression of change | Global impression of change at 1, 3, 6, and 12 months after the second injection. | 24-Months | 
| Patient Satisfaction (GPS) | Global patient satisfaction (GPS) at 1, 3, 6, and 12 months after the second injection. | 24-Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Platelet-Rich Plasma, PRP, Neutrophil-poor PRP