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

Conditions

• Osteoarthritis

Interventions

BIOLOGICAL

Leukocyte-rich PRP intra-articular injections

BIOLOGICAL

Leukocyte-poor PRP intra-articular injections

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli

  lead OTHER

Principal Investigators

• Berardo Di Matteo, MD · I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

• Alessandro Di Martino, MD · I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

• Francesco Tentoni, MD · I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

• Alice Roffi, BA · Rizzoli Orthopaedic Institute, Bologna, Italy

• Elizaveta Kon, MD · I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-09-26

Primary Completion

2017-09-26

Completion

2021-05-27

Countries

• Italy

Study Locations