Comparative Evaluation of the Performance and Safety of A-CP HA Kit, for the Preparation of a Combination of Platelet Rich Plasma and Hyaluronic Acid, Versus Hyaluronic Acid Alone and Placebo in Patients With Knee Osteoarthritis
试验速览
- 阶段
- 不适用
- 发起方
- Regen Lab SA
- 入组人数
- 290
- 试验地点
- 1
- 主要终点
- Variation in pain at walking (WOMAC A1 score)
研究概览
简要总结
Hyaluronic acid (HA) is a major component of synovial fluid, to which it confers viscosity and elasticity. It has been shown that the rheological properties of the synovial fluid decrease in patients with osteoarthritis. Intra-articular injections of hyaluronic acid represents a commonly used therapeutic option to relieve osteoarthritic symptoms, by exerting a mechanical action on cartilaginous structures of the joints, thus leading to reduced pain and improved joint function.
Platelet-rich Plasma is an autologous product prepared from the patient's own blood. Potential benefits of platelet-rich plasma for the treatment of cartilage defects have been suggested by many in vitro and animal studies. There are an increasing number of clinical studies assessing the benefits of platelet rich plasma in the treatment of osteoarthritis, showing that platelet rich plasma improves symptoms with no serious adverse events reported.
On the basis of the above, HA and platelet-rich plasma have the potential to provide added benefits in osteoarthritis symptoms when combined, in particular in patients who have had previous intra-articular HA treatment but who are still experiencing pain. Preliminary evidence to this effect was presented at the 2014 Annual Congress of the French Rheumatology Society by a group of French investigators. Renevier and Marc enrolled patients who had not experienced adequate symptom relief from previous intra-articular HA treatment and treated them with HA plus platelet-rich plasma prepared using A-CP HA Kit. Of the 71 patients treated, approximately 90% were classified as responders based on the OMERACT-OARSI criteria.
The A-CP HA Kit allows for the preparation of a homogenous solution of platelet-rich plasma and HA, intended to be injected intra-articularly for the treatment of pain in osteoarthritis. In patients who had previous intra-articular HA treatment but who are still experiencing pain, treatment with HA plus platelet rich plasma could provide a safe and reproducible option before surgery.
详细描述
Osteoarthritis (OA) is a degenerative disease of the joint cartilage. The evolution of this condition is characterized by the following symptoms: pain, joint cracking/popping, stiffness, deformity, loss of mobility and especially in the case of knee osteoarthritis, swelling (synovial effusion).
Osteoarthritis can lead to functional impairment and deformities thereby causing degradation of quality of life and may result in disabilities. Due to the fact that the knees and hips are weight bearing, osteoarthritis of these joints is often more disabling for persons who are affected by this condition.
Osteoarthritis is the most common joint disorder in the United States. Among adults 60 years of age or older, the prevalence of symptomatic knee osteoarthritis is approximately 10% in men and 13% in women. The number of people affected with symptomatic OA is likely to increase due to the aging of the population and the obesity epidemic.
A healthy joint is composed of two bone ends covered by cartilage (hyaline cartilage). This allows for shock absorption and for the bones to slide over one another with ease, thus ensuring the joint mobility. Synovial fluid (synovium) that surrounds the cartilage acts as lubrication and nutrition for the articular cartilage. It is mainly composed of hyaluronic acid, a glycosaminoglycan which binds to water molecules which in turn will result in a very viscous solution thereby giving the synovial fluid its shock absorbing properties. It has been shown that the rheological properties of synovial fluid decrease with age and in patients suffering from osteoarthritis, which may cause symptoms of pain and physical loss of function as seen in gonarthrosis, for example.
Osteoarthritis has multiple causative agents, many of which are not yet fully understood. However, a number of risk factors including age, gender, genetics, obesity, joint trauma, certain sports or professional activities are currently known. Conventionally, there is a distinction between so-called primary osteoarthritis, for which there is no obvious predisposition (of unknown origin) and secondary osteoarthritis, related to previous trauma or joint diseases. The secondary type represents the most common form of 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
- Double (Participant, 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
- •Osteoarthritis grade 2-3 according to the Kellgren & Lawrence grading scale, as defined on knee radiographs (less than 3 months old: face view, schuss view, profile and patellar axial view at 30°)
- •Knee Pain level of at least 3 on the 0-10-point WOMAC A subscale
- •Bilateral osteoarthritis provided that the contralateral knee has a pain no more than 2 on the 0-10 point scale, and not requiring systemic analgesic treatment except paracetamol until the maximum dose of 4g per day
排除标准
- •Grade <2 or >3 OA according to the Kellgren and Lawrence grading scale
- •Bilateral osteoarthritis provided that the contralateral knee has a pain more than 2 on the 0-10 point scale and requiring systemic analgesic treatment or paracetamol more than 4g per day
- •Viscosupplementation in the treatment site in the past 3 months
- •Corticosteroid injection in the treatment site in the previous 3 months
- •Systematic use of corticosteroid (except those that are inhaled) within 3 months
- •History of allergy to hyaluronic acid
- •Rheumatological disorders
- •Clinical evidence of local inflammation such as redness or heat of the joint
- •Current or medical history of autoimmune disease
- •Surgery or arthroscopy surgery in the affected knee in the past 3 months
- •Local infection in the affected knee
- •Hematologic or clotting disorders (thrombocytopenia) or blood coagulation (deficit-blood dyscrasia)
- •Anaemia (Haemoglobin < 10g/dl)
- •Platelet count below 150/mmc
- •Anticoagulant treatment
- •Viral disease (hepatitis, herpes, varicella, zona, etc.)
- •Renal failure or hemodialysis
- •Acute infection
- •Immunosuppressive states
- •Malignant disease
- •Recent fever (within previous 2 weeks) or serious disorders (liver disease, active gastroduodenal ulcer, digestive hemorrhage, etc.)
- •Pregnancy or breastfeeding or planning pregnancy during the course of the study
- •Immunosuppressants within the past 6 weeks or ongoing
- •Uncontrolled diabetes
- •Participation in another clinical study in the past 3 months
- •Ongoing participation in another OA clinical study
- •Fracture, skeletal dysplasia, congenital or acquired deformity that affects the knee
- •Hemoglobin A1C > 8% within 8 weeks prior to the study treatment
- •Have been given the diagnosis of fibromyalagia, neuropathic pain syndrome, or depression
- •Refusal to sign or inability to give Informed Consent
- •Inability to understand or comply with the requirements of the study
- •Any other reason which may interfere with the proper conduct of the study, in the investigator's opinion
研究组 & 干预措施
A-CP HA
Patients randomized in this group will be treated with a combination of platelet-rich plasma plus hyaluronic acid prepared with A-CP HA Kit.
干预措施: A-CP HA Kit (Device)
ArthroVisc 40
Patients randomized in this group will be treated with hyaluronic acid only (ArthroVisc 40); hyaluronic acid is the same as the one contained in the A-CP HA Kit.
干预措施: ArthroVisc 40 (Device)
Placebo
Patients randomized in this group will be treated with a saline solution.
干预措施: Placebo (Drug)
结局指标
主要结局
Variation in pain at walking (WOMAC A1 score)
时间窗: 6 Months
II t will be assessed by the mean difference on a 100-mm VAS between baseline (D0) and Month 6
Variation in overall OA-related symptoms
时间窗: 6 Months
It will be assessed by the mean difference in total WOMAC score on a 100-mm VAS between baseline and Month 6
次要结局
- Variation in overall OA-related symptoms, between baseline (D0) and Month 1 (D30), Month 2, Month 3, Month 4, and Month 12(12 Months)
- Variation in pain at walking (WOMAC A1 score), between baseline (D0) and Month 1 (Day 30), Month 2, Month 3, Month 4, and Month 12(12 Months)
- Patient's global assessment on a 7-point scale(12 Months)
- Patient's global assessment on a 7-point scale at Month 1 (D30), Month 2, Mont 3, Month 4, Month 6, and Month 12 Clinician's global assessment on a 7-point scale(12 Months)
- Variation of joint stiffness, between baseline (D0) and Month 1 (Day 30), Month 2, Month 3, Month 4, Month 6 and Month 12(12 Months)
- Variation of joint function, between baseline (D0) and Month 1 (Day 30), Month 2, Month 3, Month 4, Month 6 and Month 12(12 Months)
- % of OMERACT-OARSI responders(12 Months)
- Variation of the patient's quality of life(12 months)
- Variation of general pain, between baseline (D0) and Month 1 (Day 30), Month 2, Month 3, Month 4, Month 6 and Month 12(12 Months)
- Rescue medication(12 Months)