A Prospective, Multicenter, Randomized,Controlled Study to Compare the Safety and Performance of Cellular Matrix Device (Combination of Autologous Platelet-rich Plasma and Non-crosslinked Hyaluronic Acid) to Those of Synvisc-One (Crosslinked Hyaluronic Acid) for the Treatment of Mild to Moderate Knee Osteoarthritis
试验速览
- 阶段
- 不适用
- 发起方
- Regen Lab SA
- 入组人数
- 190
- 试验地点
- 2
- 主要终点
- Change from Baseline pain on walking (Western Ontario & McMaster Universities [WOMAC] A1 of the WOMAC questionaire) at 6 months
研究概览
简要总结
This is a non-inferiority study on 190 patients to evaluate whether a treatment based on the combination of autologous platelet-rich plasma and hyaluronic acid obtained with Cellular Matrix represents a therapeutic advantage to relieve symptoms associated with a mild to moderate knee osteoarthritis (particularly pain on walking) compared to hyaluronic acid only (Synvisc®-One).
详细描述
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 Matrix/A-CP HA Kit is a medical device manufactured by the Swiss company Regen Lab SA. Cellular Matrix/A-CP HA Kit 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •femorotibial knee osteoarthritis defined according to the American College of Rheumatology (ACR) 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 Visual Analog Scale (VAS): 50 ≤ WOMAC A1 ≤ 90) or reduced joint function (total WOMAC C score assessed or over the previous 24 hours on a 100-mm VAS: 50 ≤ WOMAC A1 ≤ 90)
- •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 femorotibial 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
排除标准
- •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 (non-steroidal anti-inflammatory drugs) 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
- •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
- •serious disorders (cardiovascular pathology, active gastroduodenal ulcer, digestive hemorrhage)
- •Patient with renal impairment (creatinine clearance below 45 ml / min)
- •Patient with liver failure, pending or who have recently received a liver transplant
- •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
- •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
结局指标
主要结局
Change from Baseline pain on walking (Western Ontario & McMaster Universities [WOMAC] A1 of the WOMAC questionaire) at 6 months
时间窗: 6 months
For each group, pain on walking will be evaluated using a 100-mm Visual Analog Scale (VAS), where 0= no pain and 100 = extreme pain
次要结局
- Change from Baseline pain on walking at 1 and 3 months(1 and 3 months)
- Change from Baseline overall knee osteoarthritis symptoms at 1, 3 and 6 Months(1, 3 and 6 months)
- Change from Baseline pain at 1, 3 and 6 Months(1, 3 and 6 months)
- Change from Baseline stiffness at 1, 3 and 6 Months(1, 3 and 6 months)
- Change from Baseline physical function at 1, 3 and 6 Months(1, 3 and 6 months)
- Change from Baseline quality of life at all time points(1, 3 and 6 months)
- Patient Global Assessment of the treatment received(1, 3 and 6 months)
- Clinician Global Assessment of the treatment received(1, 3 and 6 months)
- Percentage of OMERACT-OARSI (Outcome Measure in Rheumatology - Osteoarthitis Research Society International) responders at 1, 3 and 6 Months(1, 3 and 6 months)
- Percentage of patients requiring an injection of the combination of PRP/HA prepared with Cellular Matrix / A-CP HA at 6 Months(6 months)
- Number of local and systemic side effects throughout the study period(6 months)
- Cartilage structure(6 months)
- Rescue treatment consumption at 1, 3 and 6 Months(1, 3 and 6 months)