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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Istituto Ortopedico Rizzoli
ClinicalTrials.gov Identifier:
NCT01670578
First received: August 13, 2012
Last updated: August 20, 2012
Last verified: August 2012
  Purpose

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 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.


Condition Intervention Phase
Knee Chondropathy
Osteoarthritis, Knee
Biological: PRP
Device: Hyaluronic acid
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Platelet-rich Plasma (PRP) vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology: a Randomized Double-blind Controlled Trial

Resource links provided by NLM:


Further study details as provided by Istituto Ortopedico Rizzoli:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Patient global satisfaction for the treatment [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Pain Level on a Visual Analogue Score after each intra-articular injection [ Time Frame: 7 days after each injection ] [ Designated as safety issue: No ]
  • Swelling Level on a Visual Analogue Score after each injection [ Time Frame: 7 days after each injection ] [ Designated as safety issue: No ]
  • Number of Participants with Adverse Events [ Time Frame: 2, 6, 12 months of follow up ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
  • Swelling Duration after each injection [ Time Frame: 7 days after each injection ] [ Designated as safety issue: No ]

Enrollment: 192
Study Start Date: February 2009
Estimated Study Completion Date: August 2013
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PRP Group
Patients (n=96) randomized to this group of treatment will receive 3 blinded knee intra-articular injections of autologous Platelet-Rich Plasma one week apart each other.
Biological: PRP
Active Comparator: Hyaluronan Group
Patients (n=96) randomized to this group of treatment will receive 3 blinded knee intra-articular injections of hyaluronic acid ( Hyalubrix 30 mg/2ml, Fidia Farmaceutici Spa, Italy) one week apart each other.
Device: Hyaluronic acid
Other Name: Hyalubrix fl. 30 mg/2ml, Fidia farmaceutici Spa, Italy

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients affected by knee articular degenerative pathology with history of chronic (for at least 4 months) pain or swelling;
  • imaging findings of degenerative changes of the joint (Kellgren Lawrence 0 to III 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01670578

Locations
Italy
III Orthopaedic Clinic and Nano-biotechnology Lab, Rizzoli Orthopaedic Institute
Bologna, Emilia Romagna, Italy, 40136
Sponsors and Collaborators
Istituto Ortopedico Rizzoli
Investigators
Principal Investigator: Elizaveta Kon, MD III Orthopaedic Clinic and Nano-biotechnology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy
  More Information

Publications:

Responsible Party: Istituto Ortopedico Rizzoli
ClinicalTrials.gov Identifier: NCT01670578     History of Changes
Other Study ID Numbers: PRP2009KNEE
Study First Received: August 13, 2012
Last Updated: August 20, 2012
Health Authority: Italy: National Institute of Health

Keywords provided by Istituto Ortopedico Rizzoli:
P.R.P.
viscosupplementation
double-blind randomized
intra-articular injections
knee degenerative pathology
early osteoarthritis

Additional relevant MeSH terms:
Cartilage Diseases
Osteoarthritis
Osteoarthritis, Knee
Musculoskeletal Diseases
Connective Tissue Diseases
Arthritis
Joint Diseases
Rheumatic Diseases
Hyaluronic Acid
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014