Abstract

Title: "Efficacy of intra-articular polyvinylpyrrilidone collagen in the treatment of Kellgren-Lawrence grade II-III primary knee osteoarthritis compared to Hilano G-F 20: a controlled clinical trial."

Investigators: Efren Alberto Sanchez Campos, Multidisciplinary Center for the Specialized Development of Clinical Research in Yucatan; Gabriel Jose Horta Baas, Rheumatology Service, HGR 1, Merida, Yucatan.

Number of participating centers: One participating clinical research center with 32 randomized participants.

Theoretical framework: The loss of articular collagen occurs naturally as part of the aging process, but it intensifies with osteoarthritis (OA). OA is the most common joint disease and one of the leading causes of disability and dependency in the adult population, generating high healthcare costs. Knee osteoarthritis is gaining importance due to its increasing prevalence resulting from the rise in average life expectancy and obesity.

Cartilage loss is the main characteristic of osteoarthritis (OA). Enzymatic and inflammatory mechanisms participate in the degradation of articular cartilage, contributing to the chronic nature of OA. Because articular cartilage has a limited regenerative capacity, intra-articular medications have been developed to reduce inflammation and lead to clinical improvement in patients.

Intra-articular treatment is not recommended by guidelines as first-line therapy. However, it is recommended by some scientific societies for patients who do not experience symptomatic relief with non-pharmacological treatment, who do not respond to pharmacological treatment, or who have a contraindication for joint surgery. In this regard, the most commonly used medical devices are hyaluronic acid and its derivatives, but their use is limited by their cost, the method of administration, and conflicting evidence regarding their efficacy.

Given the important role of collagen in the proper functioning of the musculoskeletal system and the alterations in protein metabolism in osteoarthritis (OA), it seems reasonable that its intra-articular administration could slow the degenerative process. Over the past two decades, preclinical research studies have shown that Collagen-PVP stimulates cartilage regeneration at the molecular level, and research studies have demonstrated a reduction in pain and improvement in joint function in subjects with knee OA. However, major scientific societies do not mention or cannot recommend for or against the use of Collagen-PVP for the treatment of knee OA, based on a lack of high-quality studies and questions regarding its clinical relevance. According to the manufacturer's recommendations, 3 to 6 weekly injections are suggested, at the physician's discretion. However, no established dosage regimen is provided, and any such regimen should be supported by evidence-based medicine. In the context of knee osteoarthritis (OA), doubts remain regarding the efficacy of collagen-PVP. These controversies suggest that further research on the efficacy of this medication is necessary.

Furthermore, the average cost of treatment with collagen-PVP is lower than that of hyaluronate G-F 20. In the Mexican context, a cost-utility study reported that collagen-PVP represents a cost-effective alternative in the treatment of OA compared to the standard treatment recommended in national clinical guidelines.

Objective: To compare the clinical efficacy of intra-articular treatment with collagen-PVP with hyaluronate G-F 20, evaluated by the International Knee Committee (IKDC) functional scale score at 6 months in subjects with Kellgren-Lawrence grade II-III primary knee osteoarthritis residing in the Yucatán Peninsula.

Materials and Methods: A randomized, double-blind, controlled clinical trial was conducted at a single private clinical research center. The sample size will be 16 subjects per study group. Group assignment will be performed using a permuted random sampling method. Non-inferiority analysis will be based on a Student's t-test. Statistical analysis will include an intention-to-treat analysis.

Resources and Infrastructure: The Multidisciplinary Center for Specialized Clinical Research Development in Yucatán has the necessary infrastructure to perform arthrocentesis, joint infiltration, and the management of potential complications, as well as the storage, control, inventory, and preparation of medications for the clinical trial and rescue therapy. The team is qualified to carry out the study procedures. Evaluation methods primarily rely on patient-reported outcomes, and validated instruments are available for measuring the outcomes of interest.

Group Experience: The research group has the experience to conduct the proposed research project; it has training in the research field and publications in the area of clinimetric evaluation in subjects with rheumatic and other chronic diseases. It includes an Associate Researcher (Level C) who is also a member of the National System of Researchers.

Timeframe: 12 months.

Inclusion criteria:

• Voluntary acceptance to sign the informed consent form and commitment to attend all scheduled visits, follow the treatment plan, undergo medical evaluations, and complete all procedures of the clinical trial.
• Participants must be between 40 and 70 years of age at the time of signing the informed consent form.
• Clinical and radiographic diagnosis of primary knee osteoarthritis, Kellgren-Lawrence grade II and III. The reference radiographic study for Kellgren-Lawrence stratification must be no more than 6 months old.
• Presence of knee joint pain with an intensity ≥4 on a scale of 0 to 10 in question 1 of the average pain experienced during the last week of the assessment (Spanish version of the MOS Pain Severity Scale - MOS-PSS).
• Failure of conservative non-pharmacological treatment.
• Failure of pharmacological treatment with NSAIDs and/or failure of intra-articular corticosteroid treatment.
• BMI ≥25 and <45 kg/m².
• Commitment to comply with the activities and procedures of the clinical trial in a timely manner.
• Maintaining the diet and any physical activity performed by the participant prior to signing the informed consent form for the clinical trial, without radical or significant changes throughout the duration of this clinical trial.
• Women of reproductive potential must use a highly effective method of family planning.

Exclusion criteria:

• Participants with high-impact physical activity.
• Participants with acute arthritis of the knee.
• Participants on anticoagulants or with any contraindication to intra-articular infiltration (skin infection); participants requiring prophylactic doses of ASA.
• Participants treated with oral or injectable glucocorticoids within the last 90 days.
• Participants who have undergone intra-articular infiltration with glucocorticoids or viscosupplementation within the last 90 days.
• Participants who have undergone arthroscopy within the last 6 months.
• Participants with secondary osteoarthritis: Acromegaly, Hemochromatosis, and Hemophilia.
• Participants with coexisting Rheumatoid Arthritis, Axial or Peripheral Spondyloarthritis, Systemic Lupus Erythematosus, Fibromyalgia, or any other rheumatic disease that may cause secondary osteoarthritis.
• History of allergy to hyaluronic acid derivatives or any component constituent of the study treatments.
• Presence of varus or valgus deformity >15 degrees, or a flexion contracture >20 degrees.
• Women undergoing estrogen replacement therapy.
• Pregnant or breastfeeding women.
• Presence of any disease that, in the investigator's judgment, predisposes the patient to an additional risk by participating in this clinical trial (poorly controlled disease, psychiatric disorders, cancer, etc.).
• Immediate relatives (parents, spouses, siblings, children) of the research team, or any member of the research team (Conflict of interest).

IPD not be shared

Double-blind masking