Leukocyte-rich PRP vs Leukocyte-poor PRP for the Treatment of Knee Cartilage Degeneration: a Randomized Controlled Trial (PRP014)

August 3, 2021 updated by: Istituto Ortopedico Rizzoli

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

192

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Emilia Romagna
      • Bologna, Emilia Romagna, Italy, 40136
        • Rizzoli Orthopaedic Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Leukocyte-rich PRP group
Three weekly knee intra-articular injections of leukocyte-rich PRP
Biological: Leukocyte-rich PRP intra-articular injections
EXPERIMENTAL: Leukocyte-poor PRP group
Three weekly knee intra-articular injections of leukocyte-poor PRP
Biological: Leukocyte-poor PRP intra-articular injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
IKDC (International knee documentation committee) score trend over time
Time Frame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
KOOS (Knee Outcome Osteoarthritis Score) trend over time
Time Frame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
VAS (Visual Analogue Scale) for Pain trend over time
Time Frame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
Tegner Score trend over time
Time Frame: basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
basal (i.e. pre-treatment), 1 month, 2 months, 6 months and 12 months after treatment
Adverse events report during follow-up period
Time Frame: ba1 month, 2 months, 6 months and 12 months after treatment
ba1 month, 2 months, 6 months and 12 months after treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituto Ortopedico Rizzoli

Investigators

  • Study Chair: Berardo Di Matteo, MD, I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
  • Study Chair: Alessandro Di Martino, MD, I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
  • Study Chair: Francesco Tentoni, MD, I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy
  • Study Chair: Alice Roffi, BA, Rizzoli Orthopaedic Institute, Bologna, Italy
  • Principal Investigator: Elizaveta Kon, MD, I Clinic, Rizzoli Orthopaedic Institute, Bologna, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

September 26, 2016

Primary Completion (ACTUAL)

September 26, 2017

Study Completion (ACTUAL)

May 27, 2021

Study Registration Dates

First Submitted

September 30, 2016

First Submitted That Met QC Criteria

September 30, 2016

First Posted (ESTIMATE)

October 4, 2016

Study Record Updates

Last Update Posted (ACTUAL)

August 4, 2021

Last Update Submitted That Met QC Criteria

August 3, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PRP014

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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