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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01920152

Enrollment

Registered

2013-08-09

Start date

2013-08-31

Completion date

2019-12-05

Last updated

2021-03-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hip Osteoarthritis

Keywords

Hip, Chondropenia, Osteoarthritis.

Brief summary

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

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.

Interventions

BIOLOGICALPRP

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.

DEVICEHyaluronic Acid

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

30 Years to 72 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Sub-score	Baseline, Week 24	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.
Survivorship, as Measured by the Frequency of Patient Withdrawal of Their Treated Hip to Undergo Surgery (Total Hip Arthroplasty [THA] or Hip Resurfacing Procedure).	Baseline, 24 Months	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.

Secondary

Measure	Time frame	Description
Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Week 6	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.
Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Week 12	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.
Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Week 24	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.
Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores	Baseline, Month 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.
Hip Range of Motion (ROM) at Baseline	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).
Hip Range of Motion (ROM) at Week 6	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).
Hip Range of Motion (ROM) at Week 24	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).
Change in Hip Range of Motion (ROM)	Baseline, 24 Months	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).
Change in International Hip Outcome Tool (IHOT)	Baseline, 24 Months	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).
Change in Non-Arthritic Hip Score	Baseline, 24 Months	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.
Change in Flexion-Abduction-External Rotation (FABER) Test.	Baseline, 24 Months	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.
Change in Anterior Posterior (AP) Pelvis Radiograph/ Kellgren-Lawrence Grading Scale Classification.	Baseline, 24 Months	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.
Hip Range of Motion (ROM) at Week 12	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).
Western Ontario and McMaster Universities Arthritis Index (WOMAC) Scores at Baseline	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.

Other

Measure	Time frame	Description
Number of Patients With Adverse Events	Week 2-Week 3 and 6-12-18-24 months	Type, duration and trend of every adverse event for each patient will be reported

Countries

United States

Participant flow

Recruitment details

Participants were recruited from current patient population or first-time patients of the Hip Preservation Clinic or the Joint Clinic between 2013 and 2018. Participants were identified and recruited during routine office visits. The first participant was enrolled on December 5th, 2013 and the last participant was enrolled in December 2017.

Pre-assignment details

There were 63 participants assessed for eligibility. Of the 38 enrolled participants, 34 participants (36 hips) met the inclusion criteria and were randomized to treatment.

Participants by arm

Arm	Count
Autologous PRP Hip Injection Participants were randomized to this group of treatment. Participants who received 3 blinded hip intra-articular injections of autologous Platelet-Rich Plasma one week apart from each other and completed a minimum 6-week follow-up were included in the study. PRP: 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.	18
Autologous PRP Hip Injection Participants were randomized to this group of treatment. Participants who received 3 blinded hip intra-articular injections of autologous Platelet-Rich Plasma one week apart from each other and completed a minimum 6-week follow-up were included in the study. PRP: 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.	19
Hyaluronic Acid Hip Injection Participants were randomized to this group of treatment. Participants who received 3 blinded hip intra-articular injections of hyaluronic acid (SUPARTZ hyaluronate/2.5ml) one week apart each other and completed a minimum 6-week follow-up were included in the study. Hyaluronic Acid: 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.	13
Hyaluronic Acid Hip Injection Participants were randomized to this group of treatment. Participants who received 3 blinded hip intra-articular injections of hyaluronic acid (SUPARTZ hyaluronate/2.5ml) one week apart each other and completed a minimum 6-week follow-up were included in the study. Hyaluronic Acid: 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.	14
Total	64

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Withdrawal by Subject	1	2

Baseline characteristics

Characteristic	Total	Hyaluronic Acid Hip Injection	Autologous PRP Hip Injection
Age, Continuous	53.8 years STANDARD_DEVIATION 8.5	54.5 years STANDARD_DEVIATION 9	53.3 years STANDARD_DEVIATION 8.4
BMI	23.6 Kg/m^2 STANDARD_DEVIATION 2	23.5 Kg/m^2 STANDARD_DEVIATION 2	23.7 Kg/m^2 STANDARD_DEVIATION 2.1
Kellgren-Lawrence (KL) Grading Scale KL Grade 0	0 Hips	0 Hips	0 Hips
Kellgren-Lawrence (KL) Grading Scale KL Grade 1	0 Hips	0 Hips	0 Hips
Kellgren-Lawrence (KL) Grading Scale KL Grade 2	9 Hips	2 Hips	7 Hips
Kellgren-Lawrence (KL) Grading Scale KL Grade 3	24 Hips	12 Hips	12 Hips
Kellgren-Lawrence (KL) Grading Scale KL Grade 4	0 Hips	0 Hips	0 Hips
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants	1 Participants	0 Participants
Race (NIH/OMB) White	30 Participants	12 Participants	18 Participants
Region of Enrollment United States	31 participants	13 participants	18 participants
Sex: Female, Male Female	13 Participants	3 Participants	10 Participants
Sex: Female, Male Male	18 Participants	10 Participants	8 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 19	0 / 15
other Total, other adverse events	0 / 19	0 / 15
serious Total, serious adverse events	0 / 19	0 / 15

Outcome results

Primary

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.

Time frame: Baseline, Week 24

Population: The overall number analyzed decreased in the PRP group due to a participant withdrawing from the study to undergo a total hip replacement at week 12.

Arm	Measure	Group	Value (COUNT_OF_UNITS)
Autologous PRP Hip Injection	Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Sub-score	≥50% Decrease in WOMAC Pain (Worse)	0 Hips
Autologous PRP Hip Injection	Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Sub-score	≥50% Increase in WOMAC Pain (Better)	2 Hips
Hyaluronic Acid Hip Injection	Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Sub-score	≥50% Decrease in WOMAC Pain (Worse)	0 Hips
Hyaluronic Acid Hip Injection	Change in Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Sub-score	≥50% Increase in WOMAC Pain (Better)	0 Hips

Primary

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.