Leukocyte-rich PRP vs Leukocyte-poor PRP for the Treatment of Knee Cartilage Degeneration: a Randomized Controlled Trial

NCT ID: NCT02923700

Last Updated: 2021-08-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

192 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-26

Study Completion Date

2021-05-27

Brief Summary

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Platelet-rich Plasma (PRP) is the most exploited biologic agents currently used for the treatment of osteoarthritis (OA) of different joints, in particular knee OA.

In previous studies, it has been showed its potential to reduce pain and improve functional status in patients treated by simple intra-articular injections. However, there are several PRP formulation currently available in clinical use, and therefore it is very difficult to compare data coming from trials using different products. The most debated aspect concerning PRP formulation is the role of leukocytes, which might stimulate an early inflammatory response in the joint due to the release of metalloproteases and other pro-inflammatory cytokines.

The investigators hypothesized that the presence of leukocytes in PRP could be clinically relevant in terms of outcome, so the present double blind randomized controlled trial was designed to compare leukocyte-rich and leukocyte-poor PRP injections for the treatment of knee OA.

A power analysis has been performed for the primary endpoint of IKDC (International Knee Documentation Committee) subjective score improvement at the 12-month follow-up for PRP. From a pilot study, a standard deviation of 15.2 points was found. With an alpha error of 0.05, a beta error of 0.2 and a minimal clinically significant difference of 6.7 points corresponding at 1/3 of the documented mean improvement, the minimum sample size was 83 for each group. Considering a possible drop out of 15%, 96 patients per group are required for total 192 patients, selected according to well-defined inclusion criteria (see 'Eligibility criteria' section). Patients are then assigned to two different treatment groups, according to a randomization list. The first group of treatment consists of three weekly intra-articular injections of autologous leukocyte-rich PRP, whereas the second group of patients will be treated by three intra-articular injections of leukocyte-poor PRP.

PRP will be obtained with the following procedure: a 300-ml autologous venous blood sample will undergo 2 centrifugations (the first at 1480 rpm for 6 minutes to separate erythrocytes, and a second at 3400 rpm for 15 minutes to concentrate platelets) to produced 20 ml of leukocyte-rich PRP. In case of patients allocated to receive leukocyte-poor PRP, a special filter will be then used to separate leukocytes and obtain leukocyte-poor PRP.

The total amount of PRP will be divided into 4 small units of 5 ml each. One unit is sent to the laboratory for analysis of platelet concentration and for a quality test, 3 units are stored at -30° C.

One week after the PRP production, the injective treatment starts, with 3 weekly injections. At the moment of the injection the syringe is properly covered to prevent the patient from discovering the substance he was receiving. After the injection, patients are sent home with instructions to limit the use of the leg for at least 24 h and to use cold therapy/ice on the affected area to relieve pain. During this period, the use of non-steroidal medication is forbidden.

Patients are prospectively evaluated basally and at 2, 6, and 12 months of follow-up using clinical subjective scores and objective parameters to determine clinical outcome (see 'Outcome measure' section). Patient satisfaction and adverse events will be also reported. All the clinical evaluations are performed by a medical staff not involved in the injective procedure, in order to keep the study double blinded. At the end of the study, the nature of the injected substance is revealed to the patients.

Detailed Description

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Conditions

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Osteoarthritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Leukocyte-rich PRP group

Three weekly knee intra-articular injections of leukocyte-rich PRP

Group Type EXPERIMENTAL

Leukocyte-rich PRP intra-articular injections

Intervention Type BIOLOGICAL

Leukocyte-poor PRP group

Three weekly knee intra-articular injections of leukocyte-poor PRP

Group Type EXPERIMENTAL

Leukocyte-poor PRP intra-articular injections

Intervention Type BIOLOGICAL

Interventions

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Leukocyte-rich PRP intra-articular injections

Intervention Type BIOLOGICAL

Leukocyte-poor PRP intra-articular injections

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

1. patients affected by mono-lateral symptomatic knee articular degenerative pathology with history of chronic (for at least 4 months) pain or swelling;
2. imaging findings of degenerative changes of the joint (osteoarthritis or chondropathy with Kellgren Lawrence Score from 0 to 3 at X-ray evaluation).

Exclusion Criteria

* age \> 80 years;
* Kellgren-Lawrence score at X-ray evaluation \> 3;
* major axial deviation (varus \>5° , valgus \> 5°),
* systemic disorders such as diabetes, rheumatoid arthritis, haematological diseases (coagulopathy), severe cardiovascular diseases, infections, immunodepression;
* patients in therapy with anticoagulants or antiaggregants;
* use of NSAIDs in the 5 days before blood donation;
* patients with Hb values \< 11 g/dl and platelet values \< 150,000/mmc.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Istituto Ortopedico Rizzoli

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Berardo Di Matteo, MD

Role: STUDY_CHAIR

I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

Alessandro Di Martino, MD

Role: STUDY_CHAIR

I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

Francesco Tentoni, MD

Role: STUDY_CHAIR

I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

Alice Roffi, BA

Role: STUDY_CHAIR

Rizzoli Orthopaedic Institute, Bologna, Italy

Elizaveta Kon, MD

Role: PRINCIPAL_INVESTIGATOR

I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

Locations

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Rizzoli Orthopaedic Institute

Bologna, Emilia-Romagna, Italy

Site Status

Countries

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Italy

References

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Sadabad HN, Behzadifar M, Arasteh F, Behzadifar M, Dehghan HR. Efficacy of Platelet-Rich Plasma versus Hyaluronic Acid for treatment of Knee Osteoarthritis: A systematic review and meta-analysis. Electron Physician. 2016 Mar 25;8(3):2115-22. doi: 10.19082/2115. eCollection 2016 Mar.

Reference Type BACKGROUND
PMID: 27123220 (View on PubMed)

Yang J, Lu Y, Guo A. Platelet-rich plasma protects rat chondrocytes from interleukin-1beta-induced apoptosis. Mol Med Rep. 2016 Nov;14(5):4075-4082. doi: 10.3892/mmr.2016.5767. Epub 2016 Sep 23.

Reference Type BACKGROUND
PMID: 27665780 (View on PubMed)

Yin WJ, Xu HT, Sheng JG, An ZQ, Guo SC, Xie XT, Zhang CQ. Advantages of Pure Platelet-Rich Plasma Compared with Leukocyte- and Platelet-Rich Plasma in Treating Rabbit Knee Osteoarthritis. Med Sci Monit. 2016 Apr 17;22:1280-90. doi: 10.12659/msm.898218.

Reference Type BACKGROUND
PMID: 27086145 (View on PubMed)

Smyth NA, Haleem AM, Ross KA, Hannon CP, Murawski CD, Do HT, Kennedy JG. Platelet-Rich Plasma May Improve Osteochondral Donor Site Healing in a Rabbit Model. Cartilage. 2016 Jan;7(1):104-11. doi: 10.1177/1947603515599190.

Reference Type BACKGROUND
PMID: 26958322 (View on PubMed)

Di Matteo B, Loibl M, Andriolo L, Filardo G, Zellner J, Koch M, Angele P. Biologic agents for anterior cruciate ligament healing: A systematic review. World J Orthop. 2016 Sep 18;7(9):592-603. doi: 10.5312/wjo.v7.i9.592. eCollection 2016 Sep 18.

Reference Type BACKGROUND
PMID: 27672573 (View on PubMed)

van Drumpt RA, van der Weegen W, King W, Toler K, Macenski MM. Safety and Treatment Effectiveness of a Single Autologous Protein Solution Injection in Patients with Knee Osteoarthritis. Biores Open Access. 2016 Aug 1;5(1):261-8. doi: 10.1089/biores.2016.0014. eCollection 2016.

Reference Type BACKGROUND
PMID: 27668131 (View on PubMed)

Mlynarek RA, Kuhn AW, Bedi A. Platelet-Rich Plasma (PRP) in Orthopedic Sports Medicine. Am J Orthop (Belle Mead NJ). 2016 Jul-Aug;45(5):290-326.

Reference Type BACKGROUND
PMID: 27552452 (View on PubMed)

Sanchez M, Delgado D, Sanchez P, Muinos-Lopez E, Paiva B, Granero-Molto F, Prosper F, Pompei O, Perez JC, Azofra J, Padilla S, Fiz N. Combination of Intra-Articular and Intraosseous Injections of Platelet Rich Plasma for Severe Knee Osteoarthritis: A Pilot Study. Biomed Res Int. 2016;2016:4868613. doi: 10.1155/2016/4868613. Epub 2016 Jul 4.

Reference Type BACKGROUND
PMID: 27462609 (View on PubMed)

Mariani E, Canella V, Cattini L, Kon E, Marcacci M, Di Matteo B, Pulsatelli L, Filardo G. Leukocyte-Rich Platelet-Rich Plasma Injections Do Not Up-Modulate Intra-Articular Pro-Inflammatory Cytokines in the Osteoarthritic Knee. PLoS One. 2016 Jun 3;11(6):e0156137. doi: 10.1371/journal.pone.0156137. eCollection 2016.

Reference Type BACKGROUND
PMID: 27258008 (View on PubMed)

Smith PA. Intra-articular Autologous Conditioned Plasma Injections Provide Safe and Efficacious Treatment for Knee Osteoarthritis: An FDA-Sanctioned, Randomized, Double-blind, Placebo-controlled Clinical Trial. Am J Sports Med. 2016 Apr;44(4):884-91. doi: 10.1177/0363546515624678. Epub 2016 Feb 1.

Reference Type BACKGROUND
PMID: 26831629 (View on PubMed)

Di Martino A, Boffa A, Andriolo L, Romandini I, Altamura SA, Cenacchi A, Roverini V, Zaffagnini S, Filardo G. Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial. Am J Sports Med. 2022 Mar;50(3):609-617. doi: 10.1177/03635465211064303. Epub 2022 Feb 1.

Reference Type DERIVED
PMID: 35103547 (View on PubMed)

Other Identifiers

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PRP014

Identifier Type: -

Identifier Source: org_study_id

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