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

Osteoarthritis Clinical Trial

— PRP014  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02923700
• Other study ID #: PRP014
• Status: Completed
• Phase: Phase 4
• Start date: September 26, 2016
• Est. completion date: May 27, 2021

Study information

• Verified date: August 2021
• Source: Istituto Ortopedico Rizzoli
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: May 27, 2021
• Est. primary completion date: September 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Osteoarthritis

Intervention

Biological:
• Leukocyte-rich PRP intra-articular injections

• Leukocyte-poor PRP intra-articular injections

Locations

Country	Name	City	State
Italy	Rizzoli Orthopaedic Institute	Bologna	Emilia Romagna

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Ortopedico Rizzoli

Country where clinical trial is conducted

Italy, 

References & Publications (10)

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. — View Citation

Sánchez M, Delgado D, Sánchez P, Muiños-López E, Paiva B, Granero-Moltó F, Prósper F, Pompei O, Pérez 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	IKDC (International knee documentation committee) score trend over time		basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
Secondary	KOOS (Knee Outcome Osteoarthritis Score) trend over time		basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
Secondary	VAS (Visual Analogue Scale) for Pain trend over time		basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
Secondary	Tegner Score trend over time		basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
Secondary	Adverse events report during follow-up period		ba1 month, 2 months, 6 months and 12 months after treatment