Combined Use of PRP and Hyaluronic Acid for Infiltrative Treatment of Patients With Knee Osteoarthritis

Официальное название

Combined Use of PRP and Hyaluronic Acid for Infiltrative Treatment of Patients With Knee Osteoarthritis - Randomized Controlled Clinical Study

Обзор

"PRP+HA-23" is a double-blind randomized controlled clinical trial with 1:1:1 allocation. The objective of the study is to evaluate by a randomized controlled, double-blind clinical trial the efficacy and safety of viscosupplementation-associated PRP infiltration compared with PRP-only or HA-only infiltration for the treatment of patients with knee osteoarthritis.

Подробное описание

Patients with osteoarthritis of the knee will be included in a randomized controlled, double-blind study, in which one group of patients will be treated with an infiltration of PRP combined with HA (PRP + HA group), one group of patients will be treated with an infiltration of PRP alone (PRP group), and another group of patients will be treated with an infiltration of HA alone (HA group). They will be "blinded" patients, health care professionals who will assess clinical and functional outcomes (outcome assessors), and professionals who will analyze the data.

A total of 288 patients will be included, and they will undergo infiltrative treatment after collecting informed consent for study participation and biographical data.

All enrolled patients undergo transfusion evaluation and venous whole blood sampling from 30 to 60 mL depending on the patient's hematocrit. From the withdrawn blood, which will be collected in tubes of 9 mL each, fresh autologous PRP (PRP) will subsequently be obtained. To maintain study blinding, all patients will have their blood drawn but PRP will not be produced for patients randomized into the HA group.Following autologous PRP harvesting and production, patients randomized into the treatment group will undergo single intra-articular infiltration of PRP + HA; patients randomized into the control group 1, will undergo single intra-articular infiltration of PRP; and patients randomized into the control group 2, will undergo similar blood sampling as the PRP+ HA group and the PRP group to maintain blindness. They will then undergo an intra-articular infiltration of HA .Patients will be clinically evaluated before the infiltration procedure and at 1-3-6- 12 and 24 months after treatment by medical personnel. Questionnaires will be administered for clinical evaluations before treatment and at the above-mentioned clinical checks during follow-up

Вмешательства

• Комбинированный продукт PRP + HA injection
  Following autologous PRP harvesting and production, 5 mL of PRP and 40 mg/2 mL of HA will be infiltrated into the knee joint affected by gonarthrosis. The combined procedure will be performed by first infiltrating the hyaluronic acid, and next, leaving the needle inserted into the joint to avoid a second needle insertion, the PRP will be infiltrated, respecting the conditions of sterility. In this way, the two products will not be mixed in the same syringe.
• Биопрепарат PRP injection
  Following autologous PRP harvesting and production, patients randomized into control group 1 will undergo single intra-articular PRP infiltration. Five mL of PRP will be infiltrated into the knee joint affected by gonarthrosis.
• Устройство HA injection
  Patients randomized into control group 2, will undergo similar blood sampling as the PRP+ HA group and the PRP group to maintain blinding. They will then undergo intra-articular infiltration of 40 mg/ 2 ml HA into the knee with gonarthrosis.

Первичные конечные точки

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Срок оценки: 12 months]

Вторичные конечные точки (12)

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [Срок оценки: baseline, 1,3,6 and 24 months]
• IKDC-Subjective Score (Subjective International Knee Documentation Committee) [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Objective parameters- Range of Motion [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Objective parameters - Circumferences [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Knee Injury and Osteoarthritis Outcome Score (KOOS) [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Visual Analogue Scale (VAS) (rest) [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Visual Analogue Scale (VAS) (exercise activity) [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• EuroQol Visual Analogue Scale (EQ-VAS) [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• EQ-5D (EuroQoL) Current Health Assessment [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Tegner Activity Level Scale [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Patient Acceptable Symptom State (PASS) [Срок оценки: baseline, 1,3,6, 12 and 24 months]
• Final treatment opinion [Срок оценки: 1,3,6, 12 and 24 months]

Критерии участия

Критерии включения

• Male or female patients, aged 40 to 75 years;
• Patients with symptomatic knee osteoarthritis (VAS pain score between ≥ 3 and ≤ 8);
• Unilateral involvement of symptomatology;
• Radiographic or MRI signs of degenerative pathology of knee cartilage (Kellgren-Lawrence grade 1-3);
• Failure, defined as the persistence of symptomatology, after at least one course of conservative treatment (pharmacological, physiotherapeutic or infiltrative treatment);
• Hemoglobin > 11 g/dl; Platelet count > 150,000 plt/mm3 (Recently performed CBC examination);
• Ability and consent of patients to actively participate in clinical follow-up;
• Signature of informed consent.

Критерии исключения

• Patients unable to express consent;
• Patients undergoing intra-articular infiltration of other substance in the previous 6 months;
• Patients undergoing knee surgery in the previous 12 months;
• Patients with malignant neoplasms;
• Patients with rheumatic diseases;
• Patients with uncontrolled diabetes;
• Patients with hematological diseases (coagulopathies);
• Patients on anticoagulant-antiaggregant therapy that cannot be discontinued at the time of blood collection;
• Patients with uncompensated thyroid metabolic disorders;
• Patients abusing alcoholic beverages, drugs or medications;
• Body Mass Index > 35;
• Patients who have taken NSAIDs in the 3 days prior to blood draw;
• Patients with cardiovascular disease for whom blood sampling 30 to 60 ml would be contraindicated;
• Patients with recently performed CBC examination with Hb< 11 g/dl and Platelet values < 150,000 plt/mm3.
• Pregnant and/or fertile women.

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

Двойное слепое

Основная цель

Лечение

Центры проведения

Италия · 2 центра

• IRCCS Istituto Ortopedico Rizzoli — Bologna
• Istituto Ortopedico Rizzoli — Bologna

Публикации

• Boffa A, Salerno M, Merli G, De Girolamo L, Laver L, Magalon J, Sanchez M, Tischer T, Filardo G. Platelet-rich plasma injections induce disease-modifying effects in the treatment of osteoarthritis in animal models. Knee Surg Sports Traumatol Arthrosc. 2021 Dec;29(12):4100-4121. doi: 10.1007/s00167-021-06659-9. Epub 2021 Aug 2. PMID 34341845
• Filardo G, Previtali D, Napoli F, Candrian C, Zaffagnini S, Grassi A. PRP Injections for the Treatment of Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Trials. Cartilage. 2021 Dec;13(1_suppl):364S-375S. doi: 10.1177/1947603520931170. Epub 2020 Jun 19. PMID 32551947
• Chen WH, Lo WC, Hsu WC, Wei HJ, Liu HY, Lee CH, Tina Chen SY, Shieh YH, Williams DF, Deng WP. Synergistic anabolic actions of hyaluronic acid and platelet-rich plasma on cartilage regeneration in osteoarthritis therapy. Biomaterials. 2014 Dec;35(36):9599-607. doi: 10.1016/j.biomaterials.2014.07.058. Epub 2014 Aug 28. PMID 25176059
• Chiou CS, Wu CM, Dubey NK, Lo WC, Tsai FC, Tung TDX, Hung WC, Hsu WC, Chen WH, Deng WP. Mechanistic insight into hyaluronic acid and platelet-rich plasma-mediated anti-inflammatory and anti-apoptotic activities in osteoarthritic mice. Aging (Albany NY). 2018 Dec 23;10(12):4152-4165. doi: 10.18632/aging.101713. PMID 30582743
• Zhang Q, Liu T, Gu Y, Gao Y, Ni J. Efficacy and safety of platelet-rich plasma combined with hyaluronic acid versus platelet-rich plasma alone for knee osteoarthritis: a systematic review and meta-analysis. J Orthop Surg Res. 2022 Nov 19;17(1):499. doi: 10.1186/s13018-022-03398-6. PMID 36403041
• Lana JF, Weglein A, Sampson SE, Vicente EF, Huber SC, Souza CV, Ambach MA, Vincent H, Urban-Paffaro A, Onodera CM, Annichino-Bizzacchi JM, Santana MH, Belangero WD. Randomized controlled trial comparing hyaluronic acid, platelet-rich plasma and the combination of both in the treatment of mild and moderate osteoarthritis of the knee. J Stem Cells Regen Med. 2016 Nov 29;12(2):69-78. doi: 10.46582/js PMID 28096631

Идентификаторы

NCT: NCT06685120 · PRP+HA-23

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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