NCT01670578

Platelet-rich Plasma vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology

Platelet-rich Plasma (PRP) vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology: a Randomized Double-blind Controlled Trial

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 192 (actual)
• Sponsor: Istituto Ortopedico Rizzoli · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The investigators hypothesized that intra-articular injections of Platelet-rich Plasma (PRP) to treat knee degenerative articular cartilage pathology could determine pain relief and recovery of knee function with overall clinical outcome comparable or even better than viscosupplementation, which is a common injective approach applied in this kind of pathology. To this purpose the investigators designed a double blind randomized controlled trial comparing PRP vs viscosupplementation. 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 PRP obtained with the following procedure: a 150-ml autologous venous blood sample undergoes 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 PRP. This unit of PRP is then 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. The second treatment group consists of patients receiving three weekly injections of hyaluronic acid (Hyalubrix 30 mg/2ml, Fidia Farmaceutici Spa, Italy;Molecular Weight: 1500 kDa). To guarantee the blinding of the patients, all of them undergo blood harvesting to obtain autologous PRP which will be used only in half of them, according to the aforementioned randomization list. One week after the PRP production, the injective treatment starts, with 3 weekly injections of PRP or HA. 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.

Detailed description

Current research is investigating new methods for stimulating repair or replacing damaged cartilage. In particular, the most recent knowledge regarding tissue biology highlights a complex regulation of growth factors (GFs) for the normal tissue structure and the reaction to tissue damage. The influence of GFs on cartilage repair is now widely investigated in vitro and in vivo. Platelet Rich Plasma (PRP) is a simple, low- cost and minimally- invasive method that allows one to obtain a natural concentrate of autologous GFs from the blood, and it is increasingly applied in the clinical practice to treat knee degenerative pathology, such as chondropathy and early osteoarthritis (OA). The biological rational of PRP is that platelets contain storage pools of GFs, cytokines, chemokines and many other mediators.Although its widespread application, there are no high level studies in the literature to demonstrate the real efficacy of PRP. In fact, at the present moment, to our knowledge there is no published randomized controlled trial comparing PRP with other conservative treatments commonly used for knee OA. The investigators hypothesized that intra-articular injections of PRP to treat knee degenerative articular cartilage pathology could determine pain relief and recovery of knee function with overall clinical outcome comparable or even better than viscosupplementation, which is a common injective approach applied in this kind of pathology. To this purpose the investigators designed a double blind randomized controlled trial comparing PRP vs viscosupplementation. A power analysis has been performed for the primary endpoint of IKDC 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. 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 PRP obtained with the following procedure: a 150-ml autologous venous blood sample undergoes 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 PRP. This unit of PRP is then 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. The second treatment group consists of patients receiving three weekly injections of hyaluronic acid (Hyalubrix 30 mg/2ml, Fidia Farmaceutici Spa, Italy;Molecular Weight: 1500 kDa). To guarantee the blinding of the patients, all of them undergo blood harvesting to obtain autologous PRP which will be used only in half of them, according to the aforementioned randomization list. One week after the PRP production, the injective treatment starts, with 3 weekly injections of PRP or HA. 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. Furthermore, at the moment of each weekly injection, before injecting the substance, an attempt of harvesting synovial fluid is performed. During the same visit, also a peripheral blood sample (3 ml) is taken. These samples are then sent to a dedicated Laboratory in order to test the concentration of some GFs, pro and anti-inflammatory cytokines, both at local (synovial fluid) and systemic level (peripheral blood). The aim is to evaluate the trend in the concentration rate of these molecules over the period of the injective treatment. Patients are prospectively evaluated basally and at 2, 6, and 12 months of follow-up using IKDC, KOOS (Knee Injury and Osteoarthritis Outcome Score), EQ-VAS (Visual Analogue Scale) for general health status, and Tegner scores. Furthermore at basal evaluation and at every follow-up the ROM (Range of Motion) and the transpatellar circumference of both the index knee and the contralateral one are measured to check if any changes occurred over time. Patient satisfaction and adverse events will be also reported. During follow-up evaluations, also a peripheral blood sample is harvested (as described before) in order to assess any eventual variation in the concentration of same GFs, pro and anti-inflammatory cytokines previously evaluated. 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

• Knee Chondropathy
• Osteoarthritis, Knee

Interventions

Type	Name	Description
BIOLOGICAL	PRP
DEVICE	Hyaluronic acid

Timeline

• Start date: 2009-02-01
• Primary completion: 2013-08-01
• Completion: 2014-05-01
• First posted: 2012-08-22
• Last updated: 2017-10-30

Locations

1 site across 1 country: Italy