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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief 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

Detailed Summary:

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 clinical
Sponsor: Istituto Ortopedico Rizzoli

Current Primary Outcome: IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
• IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
• IKDC (International Knee Documentation Committee) objective score variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
• IKDC (International Knee Documentation Committee) objective score variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
• IKDC (International Knee Documentation Committee) objective score variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
• VAS (Visual Analogue scale) for General Health Status variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
• VAS (Visual Analogue scale) for General Health Status variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
• VAS (Visual Analogue scale) for General Health Status variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
• Tegner score variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
• Tegner score variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
• Tegner score variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
• KOOS (Knee injury and Osteoarthritis Outcome Score) variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
• KOOS (Knee injury and Osteoarthritis Outcome Score) variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
• KOOS (Knee injury and Osteoarthritis Outcome Score) variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
• Knee Range of Motion (ROM) variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
  Every patient had both knees' ROM measured to eventually assess any variation between the treated and un-treated knee during the follow-up evaluation
• Knee Range of Motion variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
• Knee Range of Motion variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
• Knee Trans patellar and distal quadriceps circumference variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
• Knee Trans patellar and distal quadriceps circumference variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
• Knee Trans patellar and distal quadriceps circumference variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
• Patient global satisfaction for the treatment [ Time Frame: 12 months ]
• Pain Level on a Visual Analogue Score after each intra-articular injection [ Time Frame: 7 days after each injection ]
• Swelling Level on a Visual Analogue Score after each injection [ Time Frame: 7 days after each injection ]
• Number of Participants with Adverse Events [ Time Frame: 2, 6, 12 months of follow up ]
  Type, duration and trend of every adverse event for each patient will be reported
• Pain Duration after each intra-articular injection [ Time Frame: 7 days after each injection ]
• Swelling Duration after each injection [ Time Frame: 7 days after each injection ]
• Trend in the concentration of GFs and cytokines in synovial fluid [ Time Frame: Baseline, day 7 (second injection), day 14 (third injection) ]
• Trend in the concentration of GFs and cytokine
  
  

  Original Secondary Outcome:

  • IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
  • IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
  • IKDC (International Knee Documentation Committee) objective score variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
  • IKDC (International Knee Documentation Committee) objective score variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
  • IKDC (International Knee Documentation Committee) objective score variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
  • VAS (Visual Analogue scale) for General Health Status variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
  • VAS (Visual Analogue scale) for General Health Status variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
  • VAS (Visual Analogue scale) for General Health Status variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
  • Tegner score variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
  • Tegner score variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
  • Tegner score variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
  • KOOS (Knee injury and Osteoarthritis Outcome Score) variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
  • KOOS (Knee injury and Osteoarthritis Outcome Score) variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
  • KOOS (Knee injury and Osteoarthritis Outcome Score) variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
  • Knee Range of Motion (ROM) variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
    Every patient had both knees' ROM measured to eventually assess any variation between the treated and un-treated knee during the follow-up evaluation
  • Knee Range of Motion variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
  • Knee Range of Motion variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
  • Knee Trans patellar and distal quadriceps circumference variation for both groups of treatment at 12 months of follow-up (f-up) [ Time Frame: baseline and 12 months of follow-up ]
  • Knee Trans patellar and distal quadriceps circumference variation for both groups of treatment at 6 months of follow-up (f-up) [ Time Frame: baseline and 6 months of follow-up ]
  • Knee Trans patellar and distal quadriceps circumference variation for both groups of treatment at 2 months of follow-up (f-up) [ Time Frame: baseline and 2 months of follow-up ]
  • Patient global satisfaction for the treatment [ Time Frame: 12 months ]
  • Pain Level on a Visual Analogue Score after each intra-articular injection [ Time Frame: 7 days after each injection ]
  • Swelling Level on a Visual Analogue Score after each injection [ Time Frame: 7 days after each injection ]
  • Number of Participants with Adverse Events [ Time Frame: 2, 6, 12 months of follow up ]
    Type, duration and trend of every adverse event for each patient will be reported
  • Pain Duration after each intra-articular injection [ Time Frame: 7 days after each injection ]
  • Swelling Duration after each injection [ Time Frame: 7 days after each injection ]
  
  
  Information By: Istituto Ortopedico Rizzoli
  

  Dates:
  Date Received: August 13, 2012
  Date Started: February 2009
  Date Completion:
  Last Updated: May 23, 2016
  Last Verified: May 2014