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