Efficacy of Therapy With PRP Injections Versus HA in Patients With Advanced Grade of GONArthrosis

Official title

Efficacy of Therapy With Intra-articular Injections of PRP Compared With Therapy With Intra-articular Injections of HA, in Patients With Grade III or IV GONArthrosis: a Prospective Randomized Open-label Study

Overview

Gonarthrosis is a chronic pathology affecting the knee joint and tissues. It is characterized by progressive degeneration of articular cartilage, bone and surrounding structures. Diagnosis is based on clinical, biological and radiological criteria. When knee osteoarthritis becomes symptomatic, it leads to pain associated with stiffness and functional discomfort, impacting on patients' quality of life. Patients become sedentary and isolated, which has cardiovascular and psychological consequences, with a proven excess mortality rate. To date, there are no curative treatments for gonarthrosis. Available treatments are generally aimed at relieving pain, improving joint function and slowing disease progression. Therapeutic approaches most often combine non-pharmacological treatments such as dietary measures, regular physical activity and therapeutic education, with pharmacological treatments: paracetamol, non-steroidal anti-inflammatory drugs, opioids, intra-articular injections of corticosteroids, hyaluronic acid (HA), Platelet Rich Plasma (PRP)... If these are ineffective, particularly in advanced stages (grades III-IV), then surgery for prosthesis is necessary. However, surgery is not an option for all patients, particularly those with co-morbidities, the elderly or those who refuse it. The osteoarthritis section of the French rheumatology society has drawn up recommendations, with a view to positioning these treatments, standardizing practices and improving the management of gonarthrosis patients in France. These point out that further studies are needed to validate the efficacy of certain treatments, notably intra-articular PRP injections, which are nevertheless widely used in current practice and defended by a consensus of French experts published in 2021. Indeed, the results of several therapeutic trials and meta-analyses already published show that its efficacy is often superior to that of HA, particularly in terms of symptom improvement and over a longer duration. In order to make the case for their use to learned societies, literature data must be enriched, particularly with regard to advanced stages of gonarthrosis, i.e. stages III-IV, which are the most painful. The aim is to propose an effective treatment to relieve the symptoms of patients for whom surgery is not an option.

Detailed description

In the PAGONA project, the investigators intend to use validated tools (WOMAC questionnaire, EVA scale, EQ-5D-5L quality of life questionnaire) to compare the effect of intra-articular injections of PRP with those of HA on the functional impact of the disease in patients with symptomatic knee osteoarthritis of moderate to severe stages (III-IV), by following these patients for 12 months after their last injection. The investigators plan to conduct a randomized, open-label study at the "Unité de Médecine et de Traumatologie du Sport" (UMTS) at Hôpital Sainte Musse in Toulon, where gonarthrosis treatment using intra-articular injections of PRP and HA is standard practice.

Interventions

• Procedure intra-articular injection of HA
  3 injections at 7-day intervals
• Procedure intra-articular injection of PRP
  3 injections at 15-day intervals

Primary outcome measures

• Functional impact [Time frame: 3 months after the last intra-articular injection]

Secondary outcome measures (5)

• Functional impact [Time frame: up to 12 months]
• Pain evaluation [Time frame: up to 12 months]
• Failure rate [Time frame: up to 12 months]
• Quality of life evaluation [Time frame: up to 12 months]
• Adverse events [Time frame: up to 12 months]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years ;
• MRI confirmed grade III or IV unilateral gonarthrosis ;
• Pain ≥ 3/10 on the visual analogue scale (VAS);
• Patient with a BMI < 35
• Patient capable of giving consent prior to participation in the study;
• Affiliated or entitled under a social security scheme.

Exclusion criteria

• Non-steroidal anti-inflammatory drugs\* or corticosteroids\*\* taken in the 7 days prior to inclusion;
• Local injection of hyaluronic acid in the 2 months prior to inclusion;
• Local injection of PRP within 1 year prior to inclusion;
• Local injection of corticosteroids within 5 months prior to inclusion;
• Current anticoagulant treatment that cannot be stopped during the hyaluronic acid or PRP injection protocol period;
• Patient diagnosed with any type of cancer in the last 3 years;
• Pregnant women, women in labour or breast-feeding women;
• Patients under judicial protection (guardianship, curatorship, etc.) or safeguard of justice;
• Any other reason which, in the opinion of the investigator, could interfere with the evaluation of the study objectives.

• Acetylsalicylic acid is allowed when it is prescribed as an antiplatelet agent at doses lower than or equal to 160 mg per day. It has, indeed, no anti-inflammatory effect at these doses.

• Corticosteroids can be administered when they have a local action different from the one applied to the treated knee (cutaneous, instiled or inhaled routes).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• Centre Hospitalier Intercommunal de Toulon- La Seyne sur Mer - Hôpital Sainte Musse — Toulon

Publications

• Vincent P. Acide hyaluronique intra articulaire dans la gonarthrose: une etude long-terme, ouverte, de Phase IV, avec analyse detaillee par stade de Kellgren-Lawrence. Curr Ther Res Clin Exp. 2020 May 27;92:100588. doi: 10.1016/j.curtheres.2020.100588. eCollection 2020. PMID 32714470
• Papalia R, Torre G, Zampogna B, Vorini F, Grasso A, Denaro V. Sport activity as risk factor for early knee osteoarthritis. J Biol Regul Homeost Agents. 2019 Mar-Apr;33(2 Suppl. 1):29-37. XIX Congresso Nazionale S.I.C.O.O.P. Societa' Italiana Chirurghi Ortopedici Dell'ospedalita' Privata Accreditata. PMID 31169000
• Sellam J, Courties A, Eymard F, Ferrero S, Latourte A, Ornetti P, Bannwarth B, Baumann L, Berenbaum F, Chevalier X, Ea HK, Fabre MC, Forestier R, Grange L, Lellouche H, Maillet J, Mainard D, Perrot S, Rannou F, Rat AC, Roux CH, Senbel E, Richette P; French Society of Rheumatology. Recommendations of the French Society of Rheumatology on pharmacological treatment of knee osteoarthritis. Joint Bone PMID 32931933
• Nuesch E, Dieppe P, Reichenbach S, Williams S, Iff S, Juni P. All cause and disease specific mortality in patients with knee or hip osteoarthritis: population based cohort study. BMJ. 2011 Mar 8;342:d1165. doi: 10.1136/bmj.d1165. PMID 21385807
• Altman R, Asch E, Bloch D, Bole G, Borenstein D, Brandt K, Christy W, Cooke TD, Greenwald R, Hochberg M, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum. 1986 Aug;29(8):1039-49. doi: 10.1002/art.1780290816. PMID 3741515
• Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol. 1988 Dec;15(12):1833-40. PMID 3068365
• Zheng H, Chen C. Body mass index and risk of knee osteoarthritis: systematic review and meta-analysis of prospective studies. BMJ Open. 2015 Dec 11;5(12):e007568. doi: 10.1136/bmjopen-2014-007568. PMID 26656979
• Eymard F, Ornetti P, Maillet J, Noel E, Adam P, Legre-Boyer V, Boyer T, Allali F, Gremeaux V, Kaux JF, Louati K, Lamontagne M, Michel F, Richette P, Bard H; GRIP (Groupe de Recherche sur les Injections de PRP, PRP Injection Research Group). Intra-articular injections of platelet-rich plasma in symptomatic knee osteoarthritis: a consensus statement from French-speaking experts. Knee Surg Sports Tra PMID 32583023

Identifiers

NCT: NCT07016672 · 2024-CHITS-001 · 2024-A00370-47

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗