Clinical trial NCT02923700: Leukocyte-rich PRP vs Leukocyte-poor PRP for the Treatment of Knee Cartilage Degeneration: a Randomized Controlled Trial
Official title: Leukocyte-rich PRP vs Leukocyte-poor PRP for the Treatment of Knee Cartilage Degeneration: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Osteoarthritis
Keywords: platelet rich plasma
intra-articular injection
leukocytes
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2016-10-04
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: IKDC (International knee documentation committee) score trend over time
timeFrame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
Secondary outcomes:
measure: KOOS (Knee Outcome Osteoarthritis Score) trend over time
timeFrame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
measure: VAS (Visual Analogue Scale) for Pain trend over time
timeFrame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
measure: Tegner Score trend over time
timeFrame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
measure: Adverse events report during follow-up period
timeFrame: ba1 month, 2 months, 6 months and 12 months after treatment
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: Rizzoli Orthopaedic Institute
state: Emilia Romagna
Study officials:
affiliation: I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
name: Berardo Di Matteo, MD
role: STUDY_CHAIR
affiliation: I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
name: Alessandro Di Martino, MD
role: STUDY_CHAIR
affiliation: I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
name: Francesco Tentoni, MD
role: STUDY_CHAIR
affiliation: Rizzoli Orthopaedic Institute, Bologna, Italy
name: Alice Roffi, BA
role: STUDY_CHAIR
affiliation: I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
name: Elizaveta Kon, MD
role: PRINCIPAL_INVESTIGATOR
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