Knee Chondropathy Clinical Trial
Official title:
Platelet-rich Plasma (PRP) vs Viscosupplementation for the Treatment of Early 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 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.
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 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.
Patients are prospectively evaluated basally and at 2, 6, and 12 months of follow-up using
IKDC, KOOS, EQ-VAS for general health status, and Tegner scores. Furthermore at basal
evaluation and at every follow-up the ROM 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. 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.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01670578 -
Platelet-rich Plasma vs Viscosupplementation in the Treatment of Knee Articular Degenerative Pathology
|
Phase 4 |