Combined Use of PRP and Hyaluronic Acid for Infiltrative Treatment of Patients With Knee Osteoarthritis

NCT ID: NCT06685120

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 288 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2029-09-30

Brief Summary

"PRP+HA-23" is a double-blind randomized controlled clinical trial with 1:1:1 allocation. The objective of the study is to evaluate by a randomized controlled, double-blind clinical trial the efficacy and safety of viscosupplementation-associated PRP infiltration compared with PRP-only or HA-only infiltration for the treatment of patients with knee osteoarthritis.

Detailed Description

Patients with osteoarthritis of the knee will be included in a randomized controlled, double-blind study, in which one group of patients will be treated with an infiltration of PRP combined with HA (PRP + HA group), one group of patients will be treated with an infiltration of PRP alone (PRP group), and another group of patients will be treated with an infiltration of HA alone (HA group). They will be "blinded" patients, health care professionals who will assess clinical and functional outcomes (outcome assessors), and professionals who will analyze the data.

A total of 288 patients will be included, and they will undergo infiltrative treatment after collecting informed consent for study participation and biographical data.

All enrolled patients undergo transfusion evaluation and venous whole blood sampling from 30 to 60 mL depending on the patient's hematocrit. From the withdrawn blood, which will be collected in tubes of 9 mL each, fresh autologous PRP (PRP) will subsequently be obtained. To maintain study blinding, all patients will have their blood drawn but PRP will not be produced for patients randomized into the HA group.Following autologous PRP harvesting and production, patients randomized into the treatment group will undergo single intra-articular infiltration of PRP + HA; patients randomized into the control group 1, will undergo single intra-articular infiltration of PRP; and patients randomized into the control group 2, will undergo similar blood sampling as the PRP+ HA group and the PRP group to maintain blindness. They will then undergo an intra-articular infiltration of HA .Patients will be clinically evaluated before the infiltration procedure and at 1-3-6- 12 and 24 months after treatment by medical personnel. Questionnaires will be administered for clinical evaluations before treatment and at the above-mentioned clinical checks during follow-up

Conditions

Osteo Arthritis Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

PRP+HA injection

This group of patients randomized into the treatment group, will undergo single intra-articular injection of autologous PRP+HA

Group Type: EXPERIMENTAL

PRP + HA injection

Intervention Type: COMBINATION_PRODUCT

Following autologous PRP harvesting and production, 5 mL of PRP and 40 mg/2 mL of HA will be infiltrated into the knee joint affected by gonarthrosis. The combined procedure will be performed by first infiltrating the hyaluronic acid, and next, leaving the needle inserted into the joint to avoid a second needle insertion, the PRP will be infiltrated, respecting the conditions of sterility. In this way, the two products will not be mixed in the same syringe.

PRP injection

This group of patients randomized into the treatment group, will undergo single intra-articular injection of autologous PRP

Group Type: ACTIVE_COMPARATOR

PRP injection

Intervention Type: BIOLOGICAL

Following autologous PRP harvesting and production, patients randomized into control group 1 will undergo single intra-articular PRP infiltration. Five mL of PRP will be infiltrated into the knee joint affected by gonarthrosis.

HA injection

This group of patients randomized into the treatment group, will undergo single intra-articular injection of HA

Group Type: ACTIVE_COMPARATOR

HA injection

Intervention Type: DEVICE

Patients randomized into control group 2, will undergo similar blood sampling as the PRP+ HA group and the PRP group to maintain blinding. They will then undergo intra-articular infiltration of 40 mg/ 2 ml HA into the knee with gonarthrosis.

Interventions

PRP + HA injection

Following autologous PRP harvesting and production, 5 mL of PRP and 40 mg/2 mL of HA will be infiltrated into the knee joint affected by gonarthrosis. The combined procedure will be performed by first infiltrating the hyaluronic acid, and next, leaving the needle inserted into the joint to avoid a second needle insertion, the PRP will be infiltrated, respecting the conditions of sterility. In this way, the two products will not be mixed in the same syringe.

Intervention Type: COMBINATION_PRODUCT

PRP injection

Following autologous PRP harvesting and production, patients randomized into control group 1 will undergo single intra-articular PRP infiltration. Five mL of PRP will be infiltrated into the knee joint affected by gonarthrosis.

Intervention Type: BIOLOGICAL

HA injection

Patients randomized into control group 2, will undergo similar blood sampling as the PRP+ HA group and the PRP group to maintain blinding. They will then undergo intra-articular infiltration of 40 mg/ 2 ml HA into the knee with gonarthrosis.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Male or female patients, aged 40 to 75 years;

2. Patients with symptomatic knee osteoarthritis (VAS pain score between ≥ 3 and ≤ 8);

3. Unilateral involvement of symptomatology;

4. Radiographic or MRI signs of degenerative pathology of knee cartilage (Kellgren-Lawrence grade 1-3);

5. Failure, defined as the persistence of symptomatology, after at least one course of conservative treatment (pharmacological, physiotherapeutic or infiltrative treatment);

6. Hemoglobin > 11 g/dl; Platelet count > 150,000 plt/mm3 (Recently performed CBC examination);

7. Ability and consent of patients to actively participate in clinical follow-up;

8. Signature of informed consent.

Exclusion Criteria

1. Patients unable to express consent;

2. Patients undergoing intra-articular infiltration of other substance in the previous 6 months;

3. Patients undergoing knee surgery in the previous 12 months;

4. Patients with malignant neoplasms;

5. Patients with rheumatic diseases;

6. Patients with uncontrolled diabetes;

7. Patients with hematological diseases (coagulopathies);

8. Patients on anticoagulant-antiaggregant therapy that cannot be discontinued at the time of blood collection;

9. Patients with uncompensated thyroid metabolic disorders;

10. Patients abusing alcoholic beverages, drugs or medications;

11. Body Mass Index > 35;

12. Patients who have taken NSAIDs in the 3 days prior to blood draw;

13. Patients with cardiovascular disease for whom blood sampling 30 to 60 ml would be contraindicated;

14. Patients with recently performed CBC examination with Hb< 11 g/dl and Platelet values < 150,000 plt/mm3.

15. Pregnant and/or fertile women.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital of Ferrara

OTHER

Sponsor Role: collaborator

Istituto Ortopedico Rizzoli

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Davide Reale, MD

Role: PRINCIPAL_INVESTIGATOR

Istituto Ortopedico Rizzoli - Argenta

Locations

IRCCS Istituto Ortopedico Rizzoli

Bologna, , Italy

Countries

Italy

Central Contacts

Davide Reale, MD

Role: CONTACT

davide.reale@ior.it

0516366567

Roberta Licciardi, MSc

Role: CONTACT

roberta.licciardi@ior.it

0516366567

Facility Contacts

Davide Reale, MD

Role: primary

davide.reale@ior.it

0516366567

Roberta Licciardi, MSc

Role: backup

roberta.licciardi@ior.it

0516366567

References

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Reference Type: BACKGROUND

PMID: 34341845 (View on PubMed)

Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. Cartilage. 2021 Dec;13(1_suppl):364S-375S. doi: 10.1177/1947603520931170. Epub 2020 Jun 19.

Reference Type: BACKGROUND

PMID: 32551947 (View on PubMed)

Chen WH, Lo WC, Hsu WC, Wei HJ, Liu HY, Lee CH, Tina Chen SY, Shieh YH, Williams DF, Deng WP. Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials. 2014 Dec;35(36):9599-607. doi: 10.1016/j.biomaterials.2014.07.058. Epub 2014 Aug 28.

Reference Type: BACKGROUND

PMID: 25176059 (View on PubMed)

Chiou CS, Wu CM, Dubey NK, Lo WC, Tsai FC, Tung TDX, Hung WC, Hsu WC, Chen WH, Deng WP. Mechanistic insight into hyaluronic acid and platelet-rich plasma-mediated anti-inflammatory and anti-apoptotic activities in osteoarthritic mice. Aging (Albany NY). 2018 Dec 23;10(12):4152-4165. doi: 10.18632/aging.101713.

Reference Type: BACKGROUND

PMID: 30582743 (View on PubMed)

Zhang Q, Liu T, Gu Y, Gao Y, Ni J. Efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis. J Orthop Surg Res. 2022 Nov 19;17(1):499. doi: 10.1186/s13018-022-03398-6.

Reference Type: BACKGROUND

PMID: 36403041 (View on PubMed)

Lana JF, Weglein A, Sampson SE, Vicente EF, Huber SC, Souza CV, Ambach MA, Vincent H, Urban-Paffaro A, Onodera CM, Annichino-Bizzacchi JM, Santana MH, Belangero WD. Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee. J Stem Cells Regen Med. 2016 Nov 29;12(2):69-78. doi: 10.46582/jsrm.1202011. eCollection 2016.

Reference Type: BACKGROUND

PMID: 28096631 (View on PubMed)

Other Identifiers

PRP+HA-23

Identifier Type: -

Identifier Source: org_study_id