Clinical trial NCT05378815: Platelet-rich Plasma in Symptomatic Knee Osteoarthritis
Official title: Platelet-rich Plasma in Symptomatic Knee Osteoarthritis: a Randomized, Double-blind, Placebo-controlled, Multicentre Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Knee Osteoarthritis
Keywords: Knee osteoarthritis
Platelet rich plasma
PRP
Placebo controlled trial
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2022-05-18
Enrollment: 210
Sex: ALL
Minimum age (years): 40
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, double blinded, placebo-controlled trial comparing 3 intra-articular injections of PRP (Regenkit) and NaCl in patients with symptomatic knee osteoarthritis
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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
timeFrame: between week 0 and week 14
Secondary outcomes:
measure: Intensity of global pain in the target knee over the last 48 hours evaluated by NRS between week 0 and week 26
timeFrame: between week 0 and week 26
measure: WOMAC score
timeFrame: between week 0 and week 26
measure: OMERACT-OARSI response
timeFrame: between week 0 and week 26
measure: EQ5D-5L score
timeFrame: between week 0 and week 26
measure: Number of level 1 or 2 analgesics consumed
timeFrame: between week 0 and week 26
measure: drug dose of level 1 or 2 analgesics consumed
timeFrame: between week 0 and week 26
measure: Collection of adverse events
timeFrame: between week 0 and week 26
measure: Serum biomarker assay Coll2-1
timeFrame: between week 0 and week 14
measure: Serum biomarker assay Coll2-1 NO₂
timeFrame: between week 0 and week 14
measure: Serum biomarker assay PIIANP
timeFrame: between week 0 and week 14
Other outcomes:
Locations:
city: Créteil
country: France
facility: Florent Eymard
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Florent Eymard, MD, PhD
role: STUDY_DIRECTOR
References: