Platelet-rich Plasma in Symptomatic Knee Osteoarthritis

Официальное название

Platelet-rich Plasma in Symptomatic Knee Osteoarthritis: a Randomized, Double-blind, Placebo-controlled, Multicentre Trial

Обзор

Intro: Platelet rich plasma (PRP) is largely used in various musculoskeletal disorders such as chronic tendinopathies but also osteoarthritis (OA). Several therapeutic trials evaluating the effectiveness of intra-articular PRP injections in knee OA as well as meta-analyses have already been published. Most of them have compared PRP to Hyaluronic Acid (HA). Their design was very heterogeneous in terms of PRP characteristics and injection protocol. Moreover, the number of patients included was often very low. Only few studies have compared PRP to placebo (physiological serum) and presented the same methodological limitations (limited number of patients, heterogeneous protocols in terms of number and frequency of injections, characteristics of PRP, etc.). Given the insufficient level of evidence related to these limitations, PRP injections are not recommended in the treatment of symptomatic knee OA by the main scientific societies such as American College of Rheumatology (ACR), Osteoarthritis Research Society International (OARSI), American Academy of Orthopedic Surgeons (AAOS) and French Society of Rheumatology (SFR). Experts in the field agree on the need for a placebo-controlled trial with hihg methodological quality and simple design in order to conclude with a good level of evidence to the benefit or not of this new therapeutic weapon in symptomatic knee osteoarthritis of moderate radiographic severity.

Подробное описание

Hypothesis/Objective:

The main objective of this trial is to assess the pain decrease over the last 48 hours assessed by simple numerical scale (NRS) at W14 after 3 weekly injections of PRP (W0, W1 and W2) compared to 3 injections of an equivalent volume of physiological serum in patients suffering from a knee osteoarthritis of moderate radiological severity \[Kellgren and Lawrence (KL) 2 or 3\].

The secondary objectives will aim to compare the decrease in the level of pain and functional assessed by NRS at W8 and W26, WOMAC scores at W8, W14 and W26, by OMERACT-OARSI response at W8, W14 and W26, in EQ5D-5L score at W8, W14 and W26 between PRN and placebo group. We will also assess the decrease in the consumption of analgesics at W8, W14 and W26 and the decrease in serum level of Coll2-1, Coll2-1 NO₂ and increase in PIIANP level at W8 and W14

Вмешательства

• Процедура PRP injection
  3 weekly intra-articular injections of 5mL PRP under ultrasound guidance
• Процедура Placebo injection
  3 weekly intra-articular injections of 5mL NaCL under ultrasound guidance

Первичные конечные точки

• Change in global pain intensity in the target knee over the past 48 hours as assessed by Numeric Rating Scale (NRS) between week 0 and week 14 [Срок оценки: between week 0 and week 14]

Вторичные конечные точки (10)

• Intensity of global pain in the target knee over the last 48 hours evaluated by NRS between week 0 and week 26 [Срок оценки: between week 0 and week 26]
• WOMAC score [Срок оценки: between week 0 and week 26]
• OMERACT-OARSI response [Срок оценки: between week 0 and week 26]
• EQ5D-5L score [Срок оценки: between week 0 and week 26]
• Number of level 1 or 2 analgesics consumed [Срок оценки: between week 0 and week 26]
• drug dose of level 1 or 2 analgesics consumed [Срок оценки: between week 0 and week 26]
• Collection of adverse events [Срок оценки: between week 0 and week 26]
• Serum biomarker assay Coll2-1 [Срок оценки: between week 0 and week 14]
• Serum biomarker assay Coll2-1 NO₂ [Срок оценки: between week 0 and week 14]
• Serum biomarker assay PIIANP [Срок оценки: between week 0 and week 14]

Критерии участия

Критерии включения

• Age between 40 and 79
• Symptomatic knee OA according to ACR criteria evolving for more than 3 months
• Predominantly femoro-tibial pain
• KL 2 or 3 on femorotibial compartment on X-rays of less than 6 months
• ENS ≥ 40/100 (with or without usual analgesic treatments)
• Failures or contraindications to conventional treatments (analgesics, NSAIDs)
• Patient able to understand the requirements of the trial and having signed a free and informed consent before entering the study
• Patient able to read and understand written instructions
• Patient able to complete the self-questionnaires
• Use of effective contraception in premenopausal women

Критерии исключения

• Other pathologies of the lower limbs interfering with the evaluation of knee osteoarthritis (symptomatic hip OA, Lumbar pain…)
• Symptomatic contralateral knee OA with NRS ≥ 40/100
• Predominant patellofemoral symptoms
• Radiographic knee OA stage 1 or 4 of KL
• Predominant radiographic patellofemoral OA
• History of target knee surgery with material
• History of inflammatory or microcrystalline rheumatism
• History of fibromyalgia
• Morbid obesity (BMI> 40kgs / m2)
• Inflammatory flare (KOFUS score ≥ 7)
• Use of opioids in the month prior to inclusion
• Patient refusing to stop NSAIDs during the study and conventional analgesics 48 hours
• History of infection of the target knee
• Presence of chondrocalcinosis on the frontal x-ray
• Previous PRP injection
• Injection of HA or CS into the target knee during the last 3 months
• History of hemostasis disorders or taking a curative dose of anticoagulant
• Treatment with antiplatelet agents \[Acetylsalicylic acid (Aspegic, Kardegic, Duoplavin, Resitune, Asasantine), Clopidogrel (Plavix, Duoplavin), Dipyridamole (Persantine, Cleridium, Asasantine)\]
• Haematological disease in progress or in remission for less than 5 years (malignant hemopathies, myelodysplasia, autoimmune thrombocytopenia)
• Thrombocytopenia (<150,000 platelets)
• Patient undergoing treatment with chemotherapy or immunosuppressive drugs
• Infection at the time of inclusion (bacterial infection and / or presence of fever and / or taking antibiotics)
• Participation in a clinical trial on knee osteoarthritis during the last year
• Participation in any clinical trial completed less than 3 months ago
• Patient whose mental state does not allow him to understand the nature, objectives and possible consequences of the study
• Patient under legal protection (curatorship or guardianship)
• Pregnant woman or planning to become pregnant during the study or breastfeeding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Франция · 2 центра

• Henri Mondor — Créteil
• Florent Eymard — Créteil

Публикации

• Eymard F, Oubaya N, Ornetti P, Sellam J, Richette P, Chevalier X; PIKOA study group. Protocol for a multicentre randomised triple-blind controlled trial assessing the clinical efficacy of intra-articular platelet-rich plasma injections versus placebo in symptomatic knee osteoarthritis (PIKOA). BMJ Open. 2024 Nov 29;14(11):e085025. doi: 10.1136/bmjopen-2024-085025. PMID 39615889

Идентификаторы

NCT: NCT05378815 · APHP200819 · 2021-A00742-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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