NCT02923700: PRP014

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

Completed Phase 4 Last updated 4 August 2021

What this trial tests

Phase 4 trial testing Leukocyte-rich PRP intra-articular injections in Osteoarthritis in 192 participants. Completed in 27 May 2021.

Timeline

26 September 2016

Primary endpoint
26 September 2017

27 May 2021

Quick facts

Lead sponsor	Istituto Ortopedico Rizzoli
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	192
Start date	26 September 2016
Primary completion	26 September 2017
Estimated completion	27 May 2021
Sites	1 location across Italy

Drugs / interventions tested

• Leukocyte-rich PRP intra-articular injections — full drug profile →
• Leukocyte-poor PRP intra-articular injections — full drug profile →

Conditions studied

• Osteoarthritis — all drugs for Osteoarthritis →

Sponsor

Istituto Ortopedico Rizzoli — full company profile →

Who can join

Adults 18 to 80, any sex, with Osteoarthritis. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Leukocyte-Rich versus Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis: A Double-Blind Randomized Trial.
   Di Martino A, Boffa A, Andriolo L, Romandini I, et al · · 2022 · cited 97× · PMID 35103547 · DOI 10.1177/03635465211064303
2. Leukocyte-Rich vs. Leukocyte-Poor Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis.
   Gupta A, Jeyaraman M, Potty AG. · · 2023 · cited 21× · PMID 36672650 · DOI 10.3390/biomedicines11010141
3. Forkhead box O proteins in chondrocyte aging and diseases.
   He Y, Zhu W, Alexander PG, Hines SE, et al · · 2025 · cited 3× · PMID 40822516 · DOI 10.1016/j.jot.2025.07.011