Clinical Investigation to Compare the Safety and Efficacy of Cellular Matrix to Those of Ostenil® Plus and to Those of PRP Only

RegenLab

Status

Unknown

Conditions

Knee Osteoarthritis

Treatments

Device: Cellular Matrix / A-CP HA

Device: Ostenil® Plus

Device: RegenKit-BCT-1

Study type

Interventional

Funder types

Industry

Identifiers

NCT02964143

2016-OA-001

Details and patient eligibility

About

Platelet-rich plasma (PRP) is an autologous product prepared from the patient's own blood, representing a powerful source of platelet-derived growth factors, particularly useful in the field of regenerative medicine. The active and sequential secretion of these growth factors induces different cell signaling cascades that activate angiogenesis, cell proliferation, cell differentiation, eventually leading to new matrix synthesis and tissue regeneration.

The potential benefits from the use of PRP for the treatment of cartilage defects rely on a number of studies conducted in validated animal models or in vitro, demonstrating the ability of PRP to stimulate collagen production and proteoglycans synthesis, as well as the proliferation and differentiation of mesenchymal stem cells into chondrocytes. Additionally, an increasing number of clinical studies shows an improvement of symptoms, most especially pain, without any occurrence of serious adverse events.

Hyaluronic acid (HA), as one of the major components of the synovial fluid surrounding the cartilage, assumes an important role in the viscoelastic properties of the articular cartilage, conferring its shock absorbing and lubricating functions.

It was demonstrated that rheological properties of synovial fluid decrease with aging and in patients suffering from osteoarthritis. Nowadays, intra-articular injections of hyaluronic acid represent a well recommended therapeutic option to relieve osteoarthritic symptoms, conferring a mechanical action on joints structures, thus leading to reduced pain and improved joint function Based on these data, it seems reasonable to hypothesize that a combination of both PRP and hyaluronic acid could provide greater benefits compared to the administration of each product alone, as their effects on osteoarthritis improvement are based on different mechanisms of action. In fact, on one side PRP promotes cartilage regeneration, while on the other side the HA acts as 3-dimensional support mesh for PRP, providing optimal release of platelets growth factors, strengthening and extending in time the activity of PRP.

Cellular MatrixTM is a CE-marked class III medical device manufactured by the Swiss company RegenLab SA. Cellular MatrixTM allows to prepare autologous PRP combined with a non-crosslinked hyaluronic acid in a safe, rapid manner and in a single step. The PRP/HA combination is intended to be injected intra-articularly, in order to relieve osteoarthritic symptoms and to improve joint mobility and function. Therefore, the PRP/HA combination might represent a novel therapeutic option for patient suffering from knee osteoarthritis.

This study will evaluate whether the effects of a PRP/HA combination prepared with Cellular Matrix™, when injected intra-articularly for the treatment of mild to moderate knee osteoarthritis, are superior to those of a well-recognized hyaluronic acid treatment (Ostenil® Plus), on one hand, and to those of PRP alone, on the other hand.

Enrollment

306 estimated patients

Sex

All

Ages

50 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Symptomatic knee osteoarthritis of a unilateral knee, characterized by pain at walking (WOMAC A1 score assessed over the previous 24 hours on a 100-mm VAS: 50 ≤ WOMAC A1 ≤ 90) or reduced joint function (total WOMAC C score assessed or over the previous 24 hours on a 100-mmVAS: 50 ≤ WOMAC A1 ≤ 90)
Femoro-tibial knee osteoarthritis defined according to ACR criteria
Bilateral knee osteoarthritis is allowed, provided the contralateral knee is characterized by a maximum pain of 30 on a 0 to 100 mm scale and doesn't require systemic analgesic treatment, with the exception of paracetamol up to the maximum dose of 4 g per day
Radiographic femoro-tibial knee osteoarthritis (radiograph not older than 3 months) Kellgren & Lawrence grades of II-III
Outpatient capable of walking 50 meters without assistance
Signature of the informed consent form
Capable of understanding the study's imperatives, as well as written instructions
Capable of filling-out evaluation questionnaires

Exclusion criteria

Radiographic femoro-tibial knee osteoarthritis Kellgren & Lawrence grades of I or IV
Bilateral knee osteoarthritis, characterized by pain greater than 30 of both knees evaluated on a 0 to 100-mm scale and requiring systemic analgesic treatment or paracetamol greater than 4g/ day
Viscosupplementation in the past 3 months
Corticosteroid injection in the past 3 months
PRP or PRP/HA injection in the past 12 months
Any surgery of the knee planned during the next 6 months
Systematic use of corticosteroids (except those that are inhaled) or level III analgesics in the past 3 months and NSAID during the past month
Treatment with slow-acting anti-rheumatic drugs (diacerhein, soybean or avocado unsaponifiables, chondroitin sulfate, glucosamine) started in the past 6 months
History of allergy to hyaluronic acid
Auto-immune disease (rheumatoid arthritis, lupus)
Surgery of the affected knee in the past 3 months
Infection of the affected knee in the past 6 months
Rheumatologic disorder other than arthritis
Clinical evidence of local inflammation such as redness or heat of the joint
Any knee surgery planned within 6 months
Hereditary or acquired hematologic or clotting disorders, such as drepanocytosis, platelet dysfunction, thrombocytopenia (<150'000 platelets/mm3), etc.
Anemia (Hemoglobin < 10g/dl)
Anticoagulant treatment (patients under antiaggregant treatment can take part to this study as long as their clotting time (CT) is within the reference value)
Acute infection
Malignant disease (especially bone and hematological)
Recent fever or serious disorders (cardiovascular pathology, active gastroduodenal ulcer, digestive hemorrhage, liver disease, etc.)
Patient with renal impairment (creatinine clearance below 45 ml / min)
Patient with liver failure, pending or who have recently received a liver transplant
Infectious diseases
Pregnancy or breastfeeding or planning pregnancy during the course of the study
Immunosuppression
Insulin-dependent diabetic patient
Participation ongoing or in the past 3 months in another clinical study
Participation to another osteoarthritis clinical study during the past year
Refusal to sign or inability to give Informed Consent
Patient unable to submit to the constraints of the protocol, including patient whose mental condition does not allow him to understand the nature, objectives and possible consequences of the study
Any other reason which, in the opinion of the investigator, may interfere with the proper conduct of the study

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

306 participants in 3 patient groups

Experimental group

Description:

Patients from this group will be treated with a combination of platelet-rich plasma (PRP) and hyaluronic acid (HA) prepared with the Cellular Matrix / A-CP HA medical device

Treatment:

Device: Cellular Matrix / A-CP HA

Control group 1

Active Comparator group

Description:

Patients from this group will be treated with a well-recognized hyaluronic acid named Ostenil® Plus

Treatment:

Device: Ostenil® Plus

Control group 2

Active Comparator group

Description:

Patients from this group will be treated with PRP alone, prepared with RegenKit-BCT-1