Knee ChondropathyPhase 4PRP2009NCT01670578
Platelet-rich Plasma vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology
A Phase 4 study testing PRP and Hyaluronic acid in people with Knee Chondropathy and Osteoarthritis, Knee, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Knee Chondropathy, Osteoarthritis, Knee
- What is being tested?
- PRP and Hyaluronic acid
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2009to May 2014
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
III Orthopaedic Clinic and Nano-biotechnology Lab, Rizzoli Orthopaedic Institute
Bologna, Emilia-Romagna, 40136
About this study
Official title: Platelet-rich Plasma (PRP) vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology: a Randomized Double-blind Controlled Trial
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.
Read more
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.
Read the 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
- Being tested
- PRP, Hyaluronic acid
- Keywords
- P.R.P., viscosupplementation, double-blind randomized, intra-articular injections, knee degenerative pathology, early osteoarthritis
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PRPBiological
Hyaluronic acidDevice
Also called Hyalubrix fl. 30 mg/2ml, Fidia farmaceutici Spa, Italy
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Hyaluronic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
IKDC (International Knee Documentation Committee) subjective score variation for both groups of treatment at 12 months of follow-up (f-up)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: baseline and 2 months of follow-up
Tegner score variation for both groups of treatment at 12 months of follow-up (f-up)
Measured: baseline and 12 months of follow-up
Tegner score variation for both groups of treatment at 6 months of follow-up (f-up)
Measured: baseline and 6 months of follow-up
Tegner score variation for both groups of treatment at 2 months of follow-up (f-up)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Every patient had both knees' ROM measured to eventually assess any variation between the treated and un-treated knee during the follow-up evaluation
Measured: baseline and 12 months of follow-up
Knee Range of Motion variation for both groups of treatment at 6 months of follow-up (f-up)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: baseline and 2 months of follow-up
Patient global satisfaction for the treatment
Measured: 12 months
Pain Level on a Visual Analogue Score after each intra-articular injection
Measured: 7 days after each injection
Swelling Level on a Visual Analogue Score after each injection
Measured: 7 days after each injection
Number of Participants with Adverse Events
Type, duration and trend of every adverse event for each patient will be reported
Measured: 2, 6, 12 months of follow up
Pain Duration after each intra-articular injection
Measured: 7 days after each injection
Swelling Duration after each injection
Measured: 7 days after each injection
Trend in the concentration of GFs and cytokines in synovial fluid
Measured: Baseline, day 7 (second injection), day 14 (third injection)
Trend in the concentration of GFs and cytokines in peripheral blood
Measured: Baseline, day 7 (second injection), day 14 (third injection), 2 months, 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2012 (estimated)
- Study startFeb 2009
- Primary completionAug 2013
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Knee ChondropathyStudies of the same condition, open and under way.
- More trials run by Istituto Ortopedico RizzoliThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Istituto Ortopedico Rizzoli
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elizaveta Kon, MD, Principal investigator, III Orthopaedic Clinic and Nano-biotechnology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01670578
- Sponsor's protocol ID
- KNEEJECT
- Acronym
- PRP2009
- Status last verified
- Oct 2017
- First submitted
- 13 Aug 2012
- Last updated
- 30 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 14523300Everts 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.
PubMed 16921694Tschon 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.
PubMed 21196289Grimaud 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.
PubMed 12486877Sanchez 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.
PubMed 12608674Hickey 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.
PubMed 12602635Sampson 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.
PubMed 21403592Wang-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.
PubMed 20714903Kon 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.
PubMed 21082164Kon 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.
PubMed 19838676Filardo 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.
PubMed 20740273Di 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.
PubMed 30545242
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Platelet-rich Plasma (PRP) vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology: a Randomized Double-blind Controlled Trial
- ClinicalTrials.gov ID
- NCT01670578
- Acronym / sponsor ID
- PRP2009 / KNEEJECT
- Conditions
- Knee Chondropathy, Osteoarthritis, Knee
- Keywords
- P.R.P., viscosupplementation, double-blind randomized, intra-articular injections, knee degenerative pathology, early osteoarthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Istituto Ortopedico RizzoliUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Aug 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 22 Aug 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PRP Group | Experimental | Biological: PRPPatients (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. |
| Hyaluronan Group | Active comparator | Device: Hyaluronic acidPatients (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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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).
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PRP | Biological | PRP Group |
| Hyaluronic acidAlso: Hyalubrix fl. 30 mg/2ml, Fidia farmaceutici Spa, Italy | Device | Hyaluronan Group |
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
28 secondary outcomes
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
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
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 cytokines in peripheral blood
Time frame: Baseline, day 7 (second injection), day 14 (third injection), 2 months, 6 months, 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2017.
- Background: PubMed 14523300Sanchez 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.
- Background: PubMed 16921694Everts 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.
- Background: PubMed 21196289Tschon 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.
- Background: PubMed 12486877Grimaud 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.
- Background: PubMed 12608674Sanchez 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.
- Background: PubMed 12602635Hickey 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.
- Background: PubMed 21403592Sampson 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.
- Background: PubMed 20714903Wang-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.
- Background: PubMed 21082164Kon 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.
- Background: PubMed 19838676Kon 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.
- Background: PubMed 20740273Filardo 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.
- Derived from this study: PubMed 30545242Di 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizaveta Kon, MD principal investigator
III Orthopaedic Clinic and Nano-biotechnology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing PRP and Hyaluronic acid in people with Knee Chondropathy and Osteoarthritis, Knee, run by Istituto Ortopedico Rizzoli at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01670578, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2017.