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

NCT01670578 | Completed Phase 4 DMC

• 1 other identifier: KNEEJECT
• Study Type: interventional
• Target: 192
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Knee Chondropathy; Osteoarthritis, Knee

Keywords

P.R.P.; viscosupplementation; double-blind randomized; intra-articular injections; knee degenerative pathology; early osteoarthritis

Outcome Measures

Primary Outcomes (1)

• IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 12 months of follow-up (f-up)

  baseline and 12 months of follow-up

Secondary Outcomes (28)

• IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 6 months of follow-up (f-up)

  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)

  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)

  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)

  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)

  baseline and 2 months of follow-up

Study Arms (2)

PRP Group

EXPERIMENTAL

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

Hyaluronan Group

ACTIVE COMPARATOR

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

Interventions

PRP BIOLOGICAL

PRP Group

Hyaluronic acid DEVICE

Also known as: Hyalubrix fl. 30 mg/2ml, Fidia farmaceutici Spa, Italy

Hyaluronan Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Istituto Ortopedico Rizzoli: lead

Study Sites (1)

III Orthopaedic Clinic and Nano-biotechnology Lab, Rizzoli Orthopaedic Institute

Bologna, Emilia-Romagna, 40136, Italy

Location

Related Publications (12)

• Sanchez M, Azofra J, Anitua E, Andia I, Padilla S, Santisteban J, Mujika I. Plasma rich in growth factors to treat an articular cartilage avulsion: a case report. Med Sci Sports Exerc. 2003 Oct;35(10):1648-52. doi: 10.1249/01.MSS.0000089344.44434.50.

  PMID: 14523300 BACKGROUND

• Everts PA, Knape JT, Weibrich G, Schonberger JP, Hoffmann J, Overdevest EP, Box HA, van Zundert A. Platelet-rich plasma and platelet gel: a review. J Extra Corpor Technol. 2006 Jun;38(2):174-87.

  PMID: 16921694 BACKGROUND

• Tschon M, Fini M, Giardino R, Filardo G, Dallari D, Torricelli P, Martini L, Giavaresi G, Kon E, Maltarello MC, Nicolini A, Carpi A. Lights and shadows concerning platelet products for musculoskeletal regeneration. Front Biosci (Elite Ed). 2011 Jan 1;3(1):96-107. doi: 10.2741/e224.

  PMID: 21196289 BACKGROUND

• Grimaud E, Heymann D, Redini F. Recent advances in TGF-beta effects on chondrocyte metabolism. Potential therapeutic roles of TGF-beta in cartilage disorders. Cytokine Growth Factor Rev. 2002 Jun;13(3):241-57. doi: 10.1016/s1359-6101(02)00004-7.

  PMID: 12486877 BACKGROUND

• Sanchez AR, Sheridan PJ, Kupp LI. Is platelet-rich plasma the perfect enhancement factor? A current review. Int J Oral Maxillofac Implants. 2003 Jan-Feb;18(1):93-103.

  PMID: 12608674 BACKGROUND

• Hickey DG, Frenkel SR, Di Cesare PE. Clinical applications of growth factors for articular cartilage repair. Am J Orthop (Belle Mead NJ). 2003 Feb;32(2):70-6.

  PMID: 12602635 BACKGROUND

• Sampson S, Reed M, Silvers H, Meng M, Mandelbaum B. Injection of platelet-rich plasma in patients with primary and secondary knee osteoarthritis: a pilot study. Am J Phys Med Rehabil. 2010 Dec;89(12):961-9. doi: 10.1097/PHM.0b013e3181fc7edf.

  PMID: 21403592 BACKGROUND

• Wang-Saegusa A, Cugat R, Ares O, Seijas R, Cusco X, Garcia-Balletbo M. Infiltration of plasma rich in growth factors for osteoarthritis of the knee short-term effects on function and quality of life. Arch Orthop Trauma Surg. 2011 Mar;131(3):311-7. doi: 10.1007/s00402-010-1167-3. Epub 2010 Aug 17.

  PMID: 20714903 BACKGROUND

• Kon E, Filardo G, Di Martino A, Marcacci M. Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use. Knee Surg Sports Traumatol Arthrosc. 2011 Apr;19(4):516-27. doi: 10.1007/s00167-010-1306-y. Epub 2010 Nov 17.

  PMID: 21082164 BACKGROUND

• Kon E, Buda R, Filardo G, Di Martino A, Timoncini A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma: intra-articular knee injections produced favorable results on degenerative cartilage lesions. Knee Surg Sports Traumatol Arthrosc. 2010 Apr;18(4):472-9. doi: 10.1007/s00167-009-0940-8. Epub 2009 Oct 17.

  PMID: 19838676 BACKGROUND

• Filardo G, Kon E, Buda R, Timoncini A, Di Martino A, Cenacchi A, Fornasari PM, Giannini S, Marcacci M. Platelet-rich plasma intra-articular knee injections for the treatment of degenerative cartilage lesions and osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2011 Apr;19(4):528-35. doi: 10.1007/s00167-010-1238-6. Epub 2010 Aug 26.

  PMID: 20740273 BACKGROUND

• Di Martino A, Di Matteo B, Papio T, Tentoni F, Selleri F, Cenacchi A, Kon E, Filardo G. Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial. Am J Sports Med. 2019 Feb;47(2):347-354. doi: 10.1177/0363546518814532. Epub 2018 Dec 13.

  PMID: 30545242 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee; Osteoarthritis

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Officials

• Elizaveta Kon, MD

  III Orthopaedic Clinic and Nano-biotechnology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2012
• First Posted: August 22, 2012
• Study Start: February 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: May 1, 2014
• Last Updated: October 30, 2017

Record last verified: 2017-10

Locations

IT (1)