HA vs PRP: Hyaluronic Acid vs Platelet Rich Plasma: Effects on Clinical Outcomes and Intra-articular Biology for the Treatment of Knee Osteoarthritis

• Sponsor: Rush University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02588872
• Collaborator: Cornell University (Other)
• Enrollment: 111
• Location: 1
• Arms: 2
• Duration (Months): 44
• Patients Per Site Per Month: 2.5

Study Details

Study Description

Brief Summary

In this, prospective, double-blind study, patients with mild to moderate symptomatic knee osteoarthritis will be randomized to receive either a series of leukocyte poor, platelet-rich plasma or hyaluronic acid injections under ultrasound guidance. Clinical data in the form of subjective outcome measures will be collected pre-treatment and at four time intervals across a 1-year period. Synovial fluid will also collected for analysis of pro- and anti-inflammatory markers pre-treatment, and at 12 and 24 weeks.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee	Biological: Platelet-rich Plasma (PRP); Biological: Hyaluronic Acid	N/A

Detailed Description

The objective of this double-blind prospective randomized clinical trial is to compare the effects of PRP to HA in patients with mild to moderate OA using biologic and clinical correlates of outcomes associated with the treatment of OA. The investigators will test the null hypothesis that there are no differences in clinical outcomes as measured by validated clinical scoring systems for OA, nor is there any difference in intra-articular biology between groups of patients treated with HA and those treated with PRP over time.

This study was a prospective, randomized, double blind, comparative clinical trial with an allocation ratio of 1:1 that underwent IRB approval at the principal institution. Between 2011 and 2014 patients will be screened for participation. All comers with a diagnosis of osteoarthritis of the knee between 18 and 80 years of age will be screened.

Treatment and Evaluation Patients who meet inclusion criteria will be randomized via an electronic randomization process into two groups: one receiving intra-articular PRP and the other, intra-articular HA. Non-clinical staff will perform randomization, clinical staff performed the injections, and results and analyses will be performed by the primary research team. Patients and the primary research team performing analysis will be blinded to assignments. All patients will undergo a 10 ml blood draw for PRP preparation and a 3 ml peripheral blood draw for a complete blood count with leukocyte differential. This will be performed on patients who received HA to maintain patient blinding and to characterize the peripheral white blood cells (WBC) and platelet counts. A complete blood count (CBC) will be completed on PRP prior to injection to evaluate the fold increase in platelet concentration and to confirm rarity of red white blood cells. A synovial fluid aspirate of approximately 2cc will be performed under ultrasound guidance just prior to each PRP or HA injection for ELISA analysis of basal and post-treatment intra-articular environment. After treatment, patients will be instructed to limit the use of the leg for at least 24 hours and use cold therapy/icing for discomfort. During this treatment period rest or mild exertion activities (such as exercise bike, aquatic therapy) are recommended, followed by gradual return to sports or recreational activities as tolerated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 111 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Hyaluronic Acid vs Platelet Rich Plasma: Prospective Double-blind Randomized Controlled Trial Comparing Clinical Outcomes and the Effects on Intra-articular Biology for the Treatment of Knee Osteoarthritis
• Study Start Date: Aug 1, 2011
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Apr 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Hyaluronic Acid (HA) Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection.	Biological: Hyaluronic Acid
Experimental: Platelet-rich Plasma (PRP) Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume.	Biological: Platelet-rich Plasma (PRP)

Outcome Measures

Primary Outcome Measures

1. International Knee Documentation Committee Score (IKDC [This will be assessed as a change from pre-treatment visit to 1 year post treatment.]

   This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.

Secondary Outcome Measures

1. Visual Analogue Scale (VAS) [This will be assessed as a change from pre-treatment visit to 1 year post treatment.]

   This is a scale from 1-100, 100 being the worst pain imaginable and 1 being no pain at all that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.

2. Western Ontario and McMaster Universities Arthritis Index [This will be assessed as a change from pre-treatment visit to 1 year post treatment. 6-weeks post-treatment, 6-months post treatment, and finally at 1-year post treatment will be documented for the purpose of trending data.]

   This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.

3. Lysholm Knee Score [This will be assessed as a change from pre-treatment visit to 1 year post treatment.]

   This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.

4. Biologic Testing of Synovial Fluid Via ELISA Assays [Primary outcome will be change from pre-treatment to 6-month post treatment.]

   ELISA analysis will be performed for the following biological markers: IL-1β, IL-1ra, IL-6, IL-8, TNFα

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 18-80 years old

• Mild to moderate unilateral, symptomatic osteoarthritis of the knee

• No recent (within 3 months) intra-articular intervention to the affected knee

Exclusion Criteria:

• Knee instability

• Varus/Valgus alignment >5 degrees

• Bilateral knee osteoarthritis

• Systemic inflammatory arthropathy

• Known history of anemia, coagulopathy, or present use of blood thinners

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612

Sponsors and Collaborators

• Rush University Medical Center
• Cornell University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Carla Edwards, Clinical Trials Investigator, Rush University Medical Center, Rush University Medical Center
• ClinicalTrials.gov Identifier: NCT02588872
• Other Study ID Numbers: 10012103-AM02
• First Posted: Oct 28, 2015
• Last Update Posted: Sep 9, 2021
• Last Verified: Sep 1, 2021

• Keywords provided by Carla Edwards, Clinical Trials Investigator, Rush University Medical Center, Rush University Medical Center: platelet-rich plasma; hyaluronic acid
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Hyaluronic Acid

Study Results

Participant Flow

Arm/Group Title	Hyaluronic Acid (HA)	Platelet-rich Plasma (PRP)
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid	Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)
Period Title: Overall Study
STARTED	59	52
COMPLETED	59	52
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Hyaluronic Acid (HA)	Platelet-rich Plasma (PRP)	Total
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid	Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)	Total of all reporting groups
Overall Participants	59	52	111
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.8 (10.5)	55.9 (10.4)	56.3 (10.4)
Sex: Female, Male (Count of Participants)
Female	30 50.8%	21 40.4%	51 45.9%
Male	20 33.9%	28 53.8%	48 43.2%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29 (6.4)	27.4 (3.9)	28.2 (5.1)

Outcome Measures

1. Primary Outcome

Title	International Knee Documentation Committee Score (IKDC
Description	This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time Frame	This will be assessed as a change from pre-treatment visit to 1 year post treatment.

Outcome Measure Data

Analysis Population Description

9 HA patients and 3 PRP from the original cohort were lost to follow up which is why 50 HA and 49 PRP patients were included in final analysis.

Arm/Group Title	Hyaluronic Acid (HA)	Platelet-rich Plasma (PRP)
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid	Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)
Measure Participants	50	49
Mean (Standard Error) [units on a scale]	65.5 (3.6)	55.8 (3.8)

2. Secondary Outcome

Title	Visual Analogue Scale (VAS)
Description	This is a scale from 1-100, 100 being the worst pain imaginable and 1 being no pain at all that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time Frame	This will be assessed as a change from pre-treatment visit to 1 year post treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hyaluronic Acid (HA)	Platelet-rich Plasma (PRP)
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid	Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)
Measure Participants	50	49
Mean (Standard Error) [units on a scale]	57.3 (3.8)	44 (4.6)

3. Secondary Outcome

Title	Western Ontario and McMaster Universities Arthritis Index
Description	This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time Frame	This will be assessed as a change from pre-treatment visit to 1 year post treatment. 6-weeks post-treatment, 6-months post treatment, and finally at 1-year post treatment will be documented for the purpose of trending data.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hyaluronic Acid (HA)	Platelet-rich Plasma (PRP)
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid	Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)
Measure Participants	50	49
Mean (Standard Error) [units on a scale]	4 (0.6)	3.02 (0.48)

4. Secondary Outcome

Title	Lysholm Knee Score
Description	This is a scale from 1-100, 100 being high function and 1 being very poor function that will be assessed via paper questionnaire at the delineated time intervals. The Primary outcome assessed will be at an average of 1-year post treatment.
Time Frame	This will be assessed as a change from pre-treatment visit to 1 year post treatment.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Hyaluronic Acid (HA)	Platelet-rich Plasma (PRP)
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid	Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)
Measure Participants	50	49
Mean (Standard Error) [units on a scale]	55.8 (3.8)	65.5 (3.6)

5. Secondary Outcome

Title	Biologic Testing of Synovial Fluid Via ELISA Assays
Description	ELISA analysis will be performed for the following biological markers: IL-1β, IL-1ra, IL-6, IL-8, TNFα
Time Frame	Primary outcome will be change from pre-treatment to 6-month post treatment.

Outcome Measure Data

Analysis Population Description

IL-1B

Arm/Group Title	Hyaluronic Acid (HA)	Platelet-rich Plasma (PRP)
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid	Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)
Measure Participants	50	49
Mean (Standard Error) [units on a scale]	0.14 (0.005)	0.34 (0.16)

Adverse Events

Arm/Group Title	Hyaluronic Acid (HA)		Platelet-rich Plasma (PRP)
Arm/Group Description	Hyaluronic acid administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of ultra high molecular weight hyaluronan (16mg) in a 2mL injection. Hyaluronic Acid		Platelet-rich plasma administered as an intra-articular injection under ultrasound guidance as a series of three weekly injections to the affected knee. 3 weekly injections are of leukocyte poor, buffer/additive free, singe spin, platelet-rich plasma averaging 4mL in volume. Platelet-rich Plasma (PRP)
All Cause Mortality
	Hyaluronic Acid (HA)		Platelet-rich Plasma (PRP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Hyaluronic Acid (HA)		Platelet-rich Plasma (PRP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/52 (0%)
Other (Not Including Serious) Adverse Events
	Hyaluronic Acid (HA)		Platelet-rich Plasma (PRP)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/52 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.