Platelet Rich Plasma vs Hyaluronic-Acid in Hip OA (Osteoarthritis)

Study Overview
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Brief Summary
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The objective of this study is to compare the clinical efficacy of intra-articular injections of autologous platelet rich plasma (PRP) vs hyaluronic acid (HA) for symptomatic early osteoarthritis (OA) of the hip. Secondarily, this study aims to determine the feasibility and safety of treating early OA of the hip with HA and PRP.

Detailed Description
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Osteoarthritis (OA) is a common, painful condition affect adults and causes mobility disability in the United States and Europe. Unfortunately, there is no agents available that halt OA progression. Analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) have suboptimal effectiveness, and there is concern of systemic side effects. A large challenge is the development of appropriate and effective therapy in patients with OA. Currently, the most suitable route for administering OA therapy appears to be intra-articular injections that allow accumulation of critical doses of the drug within the damaged area and also reduce the risk of systemic side effects. The primary objective of this study is to compare the clinical efficacy of intra-articular injections of Platelet Rich Plasma (PRP) vs. Hyaluronic Acid for symptomatic early OA of the hip. Secondarily, the study aims to evaluate the safety and feasibility of both medications delivered. Patients, which meet inclusion criteria, are confirmed eligible, and agree to enroll in the study, would be randomized and treated with either three intra-articular PRP injections or three intra-articular Hyaluronic Acid injections. If the patient has OA in both hips, they will be randomized to receive the same injection in both hips. The Primary investigator will be unblinded to the treatment that the subject is randomized to. The PI will only be involved in the initial assessment of the patient and the actual injections. All of the follow up visits, clinical assessments and outcome scores will be performed by the sub-investigator, who will also be the examining physician. The sub-investigator will be blinded to the treatment throughout the study. All of the study subjects will be blinded to which treatment that they are assigned to. Physical exams will be performed to assess range of motion of the hip joint. The difference in ranges of motion will be statistically compared at different time points between the two groups to determine the difference in improvement between the two compared to baseline. The primary efficacy outcome will be defined as the percentage of patients having a 50% decrease in the summed score for the WOMAC pain subscale from baseline to week 24. We will measure this outcome by applying the WOMAC questionnaire compared with baseline therapy. The secondary efficacy outcomes will also include IHOT and Non Arthritic Hip Score. An anterior posterior hip radiograph will be performed at 12 months and 24 months to assess Kellgren-Classification and compared to baseline.

Official Title
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A Randomized Clinical Trial Evaluating Platelet Rich Plasma Versus Hyaluronic-Acid in the Short-term Treatment of Symptomatic OA (Osteoarthritis) of the Hip

Conditions
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Hip Osteoarthritis

Intervention / Treatment
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* Biological: PRP
* Device: Hyaluronic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female age 30-72 inclusive. Symptomatic early OA of the hip (Kellgren-Lawrence Grade 1-2-3) documented by x-ray taken within the past 6 months. Women of childbearing potential will be allowed to enroll but must be willing to practice one highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS) condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or true abstinence) throughout the study. Exclusion Criteria: Patients with polyarticular disease. Patients with major conditions such as poorly control diabetes, Cardiac Heart Failure (CHF), Chronic Obstructive Pulmonary Disease (COPD) or untreated depression Patients with known blood disorders (Blood disorders (thrombopathy, thrombocytopenia, anemia with hemoglobin <9g/dL). Patients who had intra-articular treatment with steroids within 6 months of randomization in this study or received more than 3 previous intra-articular steroid injections to the effected hip. Patients who are pregnant or nursing at the time of consent. Patients with inflammatory arthritic conditions (e.g. rheumatoid arthritis) Non-English speaking patients. (Scores used for evaluation have not been validated in Spanish) Patients who had previous hip surgery Additional disabilities in any of the lower limbs that would interfere with any of the clinical assessments. Chronic use of NSAID (defined as taking NSAID regularly every week for the last 6 months), steroids or chemotherapy drugs Treatment with NSAIDs within 2 days prior to randomization in this study Patients with a BMI over 30. Due to the fact that this study utilize an injection technique which may be inaccurate in obese subjects.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 72 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous PRP Hip Injection<br>Patients randomized to this group of treatment will receive 3 blinded hip intra-articular injections of autologous Platelet-Rich Plasma one week apart from each other. | Biological: PRP<br>* Each PRP preparation requires a total of 36 ml of peripheral blood. This will be obtained via venapuncture and collected in four 9 ml extraction tubes containing 3.8% sodium citrate. The tubes are then centrifuged at 640 rpm for 8 minutes at room temperature. The 1ml plasma fraction located above the buffy coat is aspirated from each tube and dispensed into the fractioning tube. The entire PRP process takes place under laminar airflow. Immediately prior to injection, calcium chloride is is drawn up from the activator ampoule with the activation syringe and is added to the PRP fractioning tube. The activated PRP is then injected in its entirety into the hip joint under strict aseptic technique.<br>|
| Active Comparator: Hyaluronic Acid Hip Injection<br>Patients randomized to this group of treatment will receive 3 blinded hip intra-articular injections of hyaluronic acid (SUPARTZ hyaluronate/2.5ml) one week apart each other. | Device: Hyaluronic Acid<br>* Hyaluronic acid is supplied as a non-pyrogenic solution in 2.5 ml pre-filled syringes and is administered by intra-articular injection using a 22-23 gauge needle. The full 2.5 ml is injected in one joint under strict aseptic administration.<br>* Other names: SUPARTZ;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survivorship, as Measured by the Frequency of Patient Withdrawal of Their Treated Hip to Undergo Surgery (Total Hip Arthroplasty [THA] or Hip Resurfacing Procedure). | To measure duration of clinical benefit, survivorship was analyzed by investigating the frequency of patient withdrawal of their treated hip to undergo surgery (total hip arthroplasty [THA] or hip resurfacing procedure). Survivorship was evaluating hips, not patients in this outcome measure. This served as the primary outcome measure for the study. | Baseline, 24 Months | 
| Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Sub-score | The primary efficacy outcome was defined as the percentage of patients having a 50% decrease in the summed score for the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain sub-score from baseline to week 24. The WOMAC score is a normalized patient-reported outcome measure in which 0 represents the worst possible score and 100 represents the best possible score. The WOMAC is primarily used in osteoarthritis clinical trials to evaluate the effects of arthroplasty and drug interventions in patients with hip osteoarthritis. Thus, a 50% increase in the WOMAC pain sub-score would indicate reduced pain or improvement, while a 50% decrease would indicate worsening pain. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Baseline | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) score was defined as the secondary outcome measurement. The WOMAC score is a normalized patient-reported outcome measure in which 0 represents the worst possible score and 100 represents the best possible score. The WOMAC is primarily used in osteoarthritis clinical trials to evaluate the effects of arthroplasty and drug interventions in patients with hip osteoarthritis. | Baseline | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Week 6 | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) score was defined as the secondary outcome measurement. The WOMAC score is a normalized patient-reported outcome measure in which 0 represents the worst possible score and 100 represents the best possible score. The WOMAC is primarily used in osteoarthritis clinical trials to evaluate the effects of arthroplasty and drug interventions in patients with hip osteoarthritis. | Week 6 | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Week 12 | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) score was defined as the secondary outcome measurement. The WOMAC score is a normalized patient-reported outcome measure in which 0 represents the worst possible score and 100 represents the best possible score. The WOMAC is primarily used in osteoarthritis clinical trials to evaluate the effects of arthroplasty and drug interventions in patients with hip osteoarthritis. | Week 12 | 
| Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Week 24 | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) score was defined as the secondary outcome measurement. The WOMAC score is a normalized patient-reported outcome measure in which 0 represents the worst possible score and 100 represents the best possible score. The WOMAC is primarily used in osteoarthritis clinical trials to evaluate the effects of arthroplasty and drug interventions in patients with hip osteoarthritis. | Week 24 | 
| Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores | The Western Ontario and McMaster Universities Arthritis Index (WOMAC) score was defined as the secondary outcome measurement. The WOMAC score is a normalized patient-reported outcome measure in which 0 represents the worst possible score and 100 represents the best possible score. The WOMAC is primarily used in osteoarthritis clinical trials to evaluate the effects of arthroplasty and drug interventions in patients with hip osteoarthritis. | Baseline, Month 24 | 
| Hip Range of Motion (ROM) at Baseline | The range of motion (ROM) of the hip is reported for both groups of treatment. This includes external rotation (ER), internal rotation (IR), and flexion (FL). | Baseline | 
| Hip Range of Motion (ROM) at Week 6 | The range of motion (ROM) of the hip is reported for both groups of treatment. This includes external rotation (ER), internal rotation (IR), and flexion (FL). | Week 6 | 
| Hip Range of Motion (ROM) at Week 12 | The range of motion (ROM) of the hip is reported for both groups of treatment. This includes external rotation (ER), internal rotation (IR), and flexion (FL). | Week 12 | 
| Hip Range of Motion (ROM) at Week 24 | The range of motion (ROM) of the hip is reported for both groups of treatment. This includes external rotation (ER), internal rotation (IR), and flexion (FL). | Week 24 | 
| Change in Hip Range of Motion (ROM) | The range of motion (ROM) of the hip is reported for both groups of treatment. This includes external rotation (ER), internal rotation (IR), and flexion (FL). | Baseline, 24 Months | 
| Change in International Hip Outcome Tool (IHOT) | The International Hip Outcome Tool (IHOT) score is reported for both groups of treatment as the change from baseline to 24 months post-injection. The iHOT12 instrument is a joint-specific PRO for evaluating quality of life (QoL). A score of 100 indicates excellent QoL (full function and no symptoms), whereas zero signifies the worst QoL (maximum limitations and extreme symptoms). | Baseline, 24 Months | 
| Change in Non-Arthritic Hip Score | The Non Arthritic Hip subjective score is reported for both groups of treatment as the change from baseline to 24 months post-injection. The maximum score is 100 indicating normal hip function. | Baseline, 24 Months | 
| Change in Flexion-Abduction-External Rotation (FABER) Test. | The flexion-abduction-external rotation (FABER) test is a clinical test utilized as a provocation test to detect hip, lumbar spine, or sacroiliac joint pathology. A positive FABER test is one that reproduces the patient's pain or limits their range of movement, while a negative FABER test is one that does not reproduce the patient's pain or limit their range of movement. The FABER test is reported for both groups of treatment as count of hips experiencing a decrease in pain (from a positive test to a negative test) during the FABER test from baseline to 24 months. | Baseline, 24 Months | 
| Change in Anterior Posterior (AP) Pelvis Radiograph/ Kellgren-Lawrence Grading Scale Classification. | Anterior posterior hip x-rays were performed for each hip and classified according to Kellgren-Lawrence (KL) grading scale, which is defined as follows: 0 = normal; 1 = doubtful narrowing of joint space and possible osteophytic lipping; 2 = definite osteophytes and possible narrowing of joint space; 3 = moderate multiple osteophytes, definite narrowing of joint space, some sclerosis, and possible deformity of bone contour; 4 = large osteophytes, marked narrowing of joint space, severe sclerosis, and definite deformity of bone contour. The Kellgren-Lawrence (KL) Grading Scale is reported for both groups of treatment as the change from baseline to 24 months. | Baseline, 24 Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hip, Chondropenia, Osteoarthritis.