An interventional study of Leukocyte-Poor Platelet-Rich Plasma and High Molecular Weight Hyaluronic Acid in Knee Osteoarthritis, sponsored by University of Sao Paulo General Hospital. Not yet recruiting at 1 site in Brazil. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by University of Sao Paulo General Hospital · Not applicable, Interventional, and Treatment
The goal of this clinical trial is to learn whether a single knee injection of platelet-rich plasma (PRP) combined with hyaluronic acid (HA) works better than PRP alone or HA alone to relieve pain and improve function in physically active adults (athletes) with knee osteoarthritis. The main questions it aims to answer are:
Researchers will compare three groups: PRP plus HA, PRP alone and HA alone. The PRP will be leukocyte-poor, prepared fresh, standardized to at least 1,000,000 platelets per microliter and a total dose of at least 5 billion platelets, and fully characterized according to the MIBO checklist and the AAOS/NIH minimum reporting standards.
Participants will:
Background: Intra-articular platelet-rich plasma (PRP) has shown clinical benefit in mild to moderate knee osteoarthritis (OA), but results are heterogeneous. Differences in preparation, platelet concentration, injected volume, leukocyte content and absolute platelet dose make comparisons difficult, and most previous randomized trials poorly report the characteristics of the biologic product. Recent evidence suggests a relationship between higher platelet exposure and better clinical response. The combination of PRP and hyaluronic acid (HA) has shown favorable results compared with HA alone, but it remains uncertain whether the combination adds benefit to PRP alone when both are applied with standardized technique, full product characterization, blinding and long follow-up.
Population: In this study, the term athletes is used operationally to describe physically active adults who regularly practice structured exercise (at least 150 minutes per week of moderate intensity or 75 minutes per week of vigorous intensity for at least 6 months, according to the World Health Organization 2020 guidelines), confirmed by the short International Physical Activity Questionnaire (IPAQ) or a Tegner activity level of 3 or higher, and not exclusively to competitive athletes.
Design: Single-center, prospective, randomized, controlled, double-blind, superiority trial with three parallel groups (1:1:1) conducted at the Institute of Orthopaedics and Traumatology, Hospital das Clinicas, University of Sao Paulo School of Medicine (IOT-HCFMUSP), Brazil, and reported according to CONSORT 2025.
Interventions: All participants undergo blood collection to preserve blinding. Interventions are performed in a single session, intra-articularly, under ultrasound guidance, with opaque syringes. The PRP group receives approximately 5 mL of leukocyte-poor PRP; the PRP+HA group receives approximately 5 mL of leukocyte-poor PRP followed, in the same session, by a single dose of high molecular weight HA; and the HA group receives the same single dose of high molecular weight HA. The HA is a product registered with the Brazilian Health Regulatory Agency (ANVISA) and indicated for single-dose intra-articular use, with volume and concentration according to the manufacturer's specification; the same product is used for all participants, and the batch of each application is recorded. PRP is prepared at the IOT Regenerative Medicine Laboratory, used fresh and without exogenous activation, with a final concentration of at least 1,000,000 platelets/uL and a minimum total dose of 5 billion platelets. For every participant, whole blood and PRP characteristics are recorded (anticoagulant, spin protocol, platelet recovery, platelet concentration, leukocytes with differential, red blood cells, concentration factor, volume, total platelet dose, activation, delivery and post-injection care), following MIBO and the AAOS/NIH U-13 consensus. Nonsteroidal anti-inflammatory drugs must be stopped 7 days before blood collection. Acetaminophen up to 3 g/day is allowed as rescue medication, and all rescue medication use (yes/no, drug, dose and frequency) is recorded at every follow-up visit.
Randomization and blinding: The allocation sequence is generated at www.randomization.com by an independent researcher who is not involved in recruitment, interventions or assessments, using permuted blocks of 3 and 6 with randomly selected block size, stratified by sex and Kellgren-Lawrence grade (six strata). The sequence is entered into the REDCap randomization module with restricted access, and the allocation is revealed only after eligibility confirmation, informed consent and baseline assessment; sequentially numbered, opaque, sealed envelopes for each stratum are kept as a contingency. Participants, outcome assessors and the statistician are blinded. The injecting physician cannot be blinded and does not take part in outcome assessment or analysis.
Outcomes: The primary outcome is the change in WOMAC total score from baseline to 12 months, comparing PRP+HA versus PRP alone. Secondary outcomes include WOMAC total and subscales, KOOS (five subscales), Lysholm, Tegner, IKDC subjective, pain by visual analog scale (VAS), Patient Global Impression of Improvement, satisfaction, OMERACT-OARSI responder rate, rescue medication use, cointerventions, new injections, surgery and adverse events, assessed at 3, 6, 12 and 24 months, plus the association between clinical response and PRP characteristics. Questionnaires are administered electronically in REDCap, in validated Brazilian Portuguese versions, with assistance from a trained blinded assessor when needed.
Sample size and analysis: 300 participants (100 per group), assuming a clinically relevant difference of 10 points in the normalized WOMAC, standard deviation of 20 points, 80% power, adjusted significance level and up to 15% loss to follow-up. The primary analysis follows the intention-to-treat principle using analysis of covariance adjusted for baseline WOMAC and stratification factors; repeated measures are analyzed with linear mixed models, with Holm correction for multiple comparisons and multiple imputation for missing data.
3,407 studies on the registry are indexed under Osteoarthritis, Knee; 638 are open to participants now.
This study's planned enrollment of 300 is above the median of 69 across 2,822 interventional studies indexed under Osteoarthritis, Knee.
Browse Osteoarthritis, Knee studies →University of Sao Paulo General Hospital is the lead sponsor of 610 studies on the registry; 98 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 0 (0%) have results posted.
Counted across the registry records on this site, refreshed daily.
The criteria were revised on the registry on Nov 4, 2026. See what changed
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Notes: Habitual analgesics and anti-inflammatory drugs are not exclusion criteria, as they are the study rescue medications, and their use is recorded at every visit. Nonsteroidal anti-inflammatory drugs must be discontinued 7 days before blood collection; if used within this interval, the blood collection is rescheduled.
Single session: ultrasound-guided intra-articular injection of approximately 5 mL of leukocyte-poor PRP (at least 1,000,000 platelets/uL and at least 5 billion platelets), followed in the same session by a single dose of high molecular weight hyaluronic acid.
Biological: Leukocyte-Poor Platelet-Rich Plasma · Device: High Molecular Weight Hyaluronic Acid
Single session: ultrasound-guided intra-articular injection of approximately 5 mL of leukocyte-poor PRP (at least 1,000,000 platelets/uL and at least 5 billion platelets).
Biological: Leukocyte-Poor Platelet-Rich Plasma
Single session: ultrasound-guided intra-articular injection of a single dose of high molecular weight hyaluronic acid. Blood is also collected to preserve participant blinding.
Device: High Molecular Weight Hyaluronic Acid
Single ultrasound-guided intra-articular injection of approximately 5 mL of autologous leukocyte-poor platelet-rich plasma, prepared at the IOT Regenerative Medicine Laboratory, used fresh and without exogenous activation, with a final concentration of at least 1,000,000 platelets/uL and a minimum total dose of 5 billion platelets. Whole blood and PRP characteristics are recorded for every participant according to MIBO and the AAOS/NIH U-13 minimum reporting standards.
Also known as: LP-PRP
Single ultrasound-guided intra-articular injection of a single dose of high molecular weight hyaluronic acid, using a product registered with the Brazilian Health Regulatory Agency (ANVISA) and indicated for single-dose use, with volume and concentration according to the manufacturer's specification. The same product is used for all participants, and the batch of each application is recorded. In the combination group, it is administered in the same session, immediately after the PRP injection.
Also known as: Viscosupplementation
Change in WOMAC Total Score From Baseline to 12 Months
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), validated Brazilian Portuguese version. The WOMAC has 24 items (pain, 5 items; stiffness, 2 items; physical function, 17 items), each scored from 0 (none) to 4 (extreme) on a Likert scale. The total score ranges from 0 to 96 points, and higher scores indicate worse pain, stiffness and physical function (worse outcome). The outcome is the change from baseline to 12 months; a greater reduction indicates greater improvement. Primary comparison: PRP combined with hyaluronic acid versus PRP alone.
Time frame: Baseline and 12 months after the intervention
WOMAC Total and Subscale Scores (Pain, Stiffness and Physical Function)
Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), validated Brazilian Portuguese version, compared among the three groups. Total score ranges from 0 to 96; subscales range from 0 to 20 (pain), 0 to 8 (stiffness) and 0 to 68 (physical function). For the total score and all subscales, higher scores indicate worse symptoms and function (worse outcome).
Time frame: Baseline, 3, 6, 12 and 24 months after the intervention
Knee Injury and Osteoarthritis Outcome Score (KOOS)
Knee Injury and Osteoarthritis Outcome Score (KOOS), validated Brazilian Portuguese version, five subscales scored separately: pain, other symptoms, function in activities of daily living, function in sport and recreation, and knee-related quality of life. Each subscale ranges from 0 (extreme knee problems) to 100 (no knee problems); higher scores indicate better outcomes.
Time frame: Baseline, 3, 6, 12 and 24 months after the intervention
Lysholm Knee Scoring Scale
Lysholm score (0 to 100; higher scores indicate better knee function).
Time frame: Baseline, 3, 6, 12 and 24 months after the intervention
Tegner Activity Level
Tegner activity scale (0 to 10; higher levels indicate higher physical and sports activity).
Time frame: Baseline, 3, 6, 12 and 24 months after the intervention
International Knee Documentation Committee (IKDC) Subjective Knee Form
IKDC subjective score (0 to 100; higher scores indicate better knee function and fewer symptoms).
Time frame: Baseline, 3, 6, 12 and 24 months after the intervention
Knee Pain Intensity by Visual Analog Scale (VAS)
Average knee pain in the previous week on a 0 to 10 visual analog scale (0 = no pain; 10 = worst imaginable pain).
Time frame: Baseline, 3, 6, 12 and 24 months after the intervention
Patient Global Impression of Improvement (PGI-I)
Participant-rated global impression of change on a 7-point scale (1 = very much better; 7 = very much worse).
Time frame: 3, 6, 12 and 24 months after the intervention
Satisfaction With Treatment
Participant satisfaction with the treatment received on a 5-point Likert scale (1 = very dissatisfied; 5 = very satisfied).
Time frame: 3, 6, 12 and 24 months after the intervention
Proportion of OMERACT-OARSI Responders
Responders defined as improvement of at least 50% and 20 points (0 to 100 scale) in pain or function, or improvement of at least 20% and 10 points in at least two of pain, function and patient global assessment.
Time frame: 3, 6, 12 and 24 months after the intervention
Use of Rescue Medication
Use of rescue medication in each follow-up period (yes or no), drug, dose and frequency, expressed as number of days of use and cumulative dose of acetaminophen and other analgesics or anti-inflammatory drugs.
Time frame: Up to 24 months after the intervention
Cointerventions, New Injections and Knee Surgery
Number of participants with cointerventions, new intra-articular injections, surgical referral, surgery on the target knee or knee arthroplasty.
Time frame: Up to 24 months after the intervention
Incidence of Adverse Events
Number and type of adverse events, related or not to the intervention (for example, post-injection pain, effusion, stiffness, bruising, vasovagal reaction and septic arthritis), graded by severity and relationship to the procedure.
Time frame: Up to 24 months after the intervention
Association Between PRP Characteristics and Clinical Response
Association between change in WOMAC total score and PRP characteristics: platelet concentration, total platelet dose, injected volume, leukocytes, red blood cells, concentration factor and platelet recovery.
Time frame: Baseline and 12 months after the intervention
Plan to share: No — Individual participant data will not be made publicly available, in order to protect participant confidentiality in accordance with the Brazilian General Data Protection Law (LGPD) and the terms of the informed consent approved by the ethics committee. Aggregate results will be published in peer-reviewed journals.
No publications or documents are linked to this record.
Start is estimated for Apr 2027; primary completion for Dec 2029, 32 months later.
Of 1,149 non-industry interventional studies with no phase under Osteoarthritis, Knee, half reached primary completion within 17 months of starting (the median), counting those still running; a quarter within 8 and three quarters within 36. This study's planned 32 months is above that.
Counting every sponsor, half of 1,292 studies reached it within 17 months; a quarter within 8 and three quarters within 36.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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