Effect of Tergase Injection on Reducing Edema After Bilateral Total Knee Arthroplasty

Официальное название

A Randomized, Split Body, Evaluator-blinded, Trial on the Effect of Tergase Injection (Berahyaluronidase Alfa) on Reducing Edema After Both Total Knee Arthroplasty

Обзор

This clinical trial is conducted to compare and evaluate the efficacy and safety of Tergase injection (4,500 IU) in reducing postoperative edema between treated and untreated knees in patients undergoing bilateral total knee arthroplasty (TKA). Prior to participation, all subjects receive a full explanation of the study and provide voluntary written informed consent. Only subjects who meet the inclusion and exclusion criteria through screening procedures are enrolled. Enrolled subjects are randomly assigned to the experimental and control groups in a 1:1 ratio per knee, utilizing a split-body clinical trial design that compares both knees of the same subject. The analysis target is 60 knees obtained from a total of 30 subjects. According to the randomization results, the knee assigned to the experimental group receives a subcutaneous injection of 3 vials (4,500 IU) of Tergase, while the contralateral knee serves as the untreated control group. By including both the experimental and control groups within the same subject, inter-individual variation is minimized. While the investigator performing the injection is aware of the assignment, the subject remains blinded. To overcome the physical impossibility of blinding the injector due to the route of administration and drug characteristics, an 'Evaluator-Blinded' design is adopted to maintain objectivity equivalent to a double-blind study. To achieve this, the unblinded injector and the blinded evaluator who measures efficacy outcomes are strictly separated, and operational blinding is maintained by blocking information exchange between the two groups. Subjects are evaluated for efficacy and safety during hospitalization or outpatient visits at Day 1, 2, 3, 5, Week 2, Week 6, and Month 3 after bilateral TKA. Participation ends upon completion of the planned visits.

Вмешательства

• Препарат Berahyaluronidase alfa
  A total dose of 4,500 IU (3.0 mL; 3 vials) of berahyaluronidase alfa is administered subcutaneously around the suture line of the randomly assigned knee immediately after total knee arthroplasty. The dose is divided into 8 injection points, approximately 0.375 mL per point.

Первичные конечные точки

• Percent Change From Baseline in Composite Edema Index Based on Leg Circumference Measurements [Срок оценки: Baseline, Postoperative Day 2]

Вторичные конечные точки (12)

• Percent Change From Baseline in Mean Leg Circumference Swelling Rate [Срок оценки: Baseline, Postoperative Day 1, Day 3, Day 5, Week 2, Week 6, and Month 3]
• Change From Baseline in Mean Pain Intensity Score on a 0-to-10 Visual Analog Scale [Срок оценки: Baseline, Postoperative Day 1, Day 2, Day 3, Day 5, Week 2, Week 6, and Month 3]
• Change From Baseline in Active Knee Flexion Range of Motion Measured With a Goniometer [Срок оценки: Baseline, Postoperative Day 1, Day 2, Day 3, Day 5, Week 2, Week 6, and Month 3]
• Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index Total Score [Срок оценки: Baseline, Week 6, and Month 3]
• CT-Measured Mean Lower Extremity Soft Tissue Thickness at Postoperative Day 2 [Срок оценки: Postoperative Day 2]
• Change From Baseline in Serum C-Reactive Protein Concentration [Срок оценки: Baseline, Postoperative Day 1, Week 2, and Month 3]
• Change From Baseline in Serum Amyloid A Concentration [Срок оценки: Baseline, Postoperative Day 1, Week 2, and Month 3]
• Number of Participants With at Least One Predefined Postoperative Complication [Срок оценки: From immediately after surgery through postoperative Month 3]
• Number of Participants With at Least One Adverse Event [Срок оценки: From investigational product administration through postoperative Month 3]
• Number of Participants With Clinically Significant Abnormal Vital Sign Findings [Срок оценки: From Screening Visit through postoperative Month 3]
• Number of Participants With Clinically Significant Abnormal Physical Examination Findings [Срок оценки: From Screening Visit through postoperative Month 3]
• Number of Participants With Clinically Significant Abnormal Clinical Laboratory Test Results [Срок оценки: From Screening Visit through postoperative Month 3]

Критерии участия

Критерии включения

• Adult males and females aged 60 years or older and 85 years or younger.
• Patients scheduled for bilateral total knee arthroplasty due to degenerative knee osteoarthritis with a Kellgren-Lawrence grade of III or IV confirmed by imaging within the last 4 weeks.
• Patients experiencing knee joint pain of 5 or higher on a 10-point Visual Analogue Scale (VAS) during daily activities, such as walking on flat ground.
• Patients with the willingness and ability to follow the physician's instructions, including joint exercises.
• Patients classified as American Society of Anesthesiologists (ASA) Physical Status Class I or II.
• Patients who have received a full explanation of the clinical trial and have voluntarily provided written informed consent to participate.

Критерии исключения

• Participants or their family members with ongoing or a history of autoimmune diseases.
• Patients with secondary osteoarthritis of the knee.
• Patients with inflammatory arthritis (such as rheumatoid arthritis, lupus arthropathy, psoriatic arthritis) or crystal-induced arthropathy.
• Patients with a serum protein level of 5.5 g/dL or less.
• Patients with clinical laboratory results that are contraindications for total knee arthroplasty:

• WBC <3,000/μL or >12,000/μL
• CRP >10 mg/L
• Hb <10 g/dL
• Platelet count <100,000/μL
• INR >1.5
• eGFR <30 mL/min/1.73 m²
• AST or ALT >3 times the upper limit of normal
• Fasting blood glucose >200 mg/dL
• Patients with a history of drug abuse or dependence.
• Presence of local infection or sepsis in the affected lower limb, or a history of neurological abnormalities within the past 6 months.
• History of major joint surgery within 90 days.
• Patients who received systemic steroid treatment within 3 months prior to surgery.
• Patients who sustained a serious injury or received an injection in the target knee that may interfere with evaluation within 3 months prior to the screening visit.
• Patients with infections requiring hospitalization and administration of antibiotics or antimicrobics.
• Patients with any clinically significant medical condition that may interfere with study completion or outcome assessment, including but not limited to:

• Congenital heart disease, clinically significant cardiovascular disease, renal dysfunction, or uncontrolled diabetes.
• Neuromuscular disorders affecting the lower limbs.
• Severe bleeding or coagulation disorders.
• Severe knee instability that cannot be corrected with cruciate-retaining total knee arthroplasty.
• Severe knee deformity, defined as flexion contracture ≥30 degrees or varus/valgus deformity ≥30 degrees.
• Opioid dependence, defined as consumption of ≥100 mg morphine-equivalent opioids per week for more than 3 months before surgery.
• Inability to assess pain using the Visual Analogue Scale, including cognitive or language impairment.
• Venous congestion of the lower extremity.
• Morbid obesity, defined as body mass index >40 kg/m².
• History of shock or hypersensitivity to Tergase inj. or its components.
• Patients deemed unsuitable for this study by the investigator, such as those with psychiatric disorders.
• Patients currently participating in another clinical trial.

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

Простое слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Kwon H, Park HS, Shim JY, Lee KW, Choi SJ, Choi GY. Randomized, Double-Blind, Placebo-Controlled Trial on the Efficacy of Hyaluronidase in Preventing Perineal Trauma in Nulliparous Women. Yonsei Med J. 2020 Jan;61(1):79-84. doi: 10.3349/ymj.2020.61.1.79. PMID 31887803
• Alam M, Hughart R, Geisler A, Paghdal K, Maisel A, Weil A, West DP, Veledar E, Poon E. Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler Nodules: A Randomized Clinical Trial. JAMA Dermatol. 2018 Jul 1;154(7):765-772. doi: 10.1001/jamadermatol.2018.0515. PMID 29710212
• Kwoen MJ, Choi YH, Kim KS, Chang NH, Kim YK, Lee HJ. Efficacy of local hyaluronidase administration in guided bone regeneration surgery: a randomized controlled trial. J Korean Assoc Oral Maxillofac Surg. 2021 Apr 30;47(2):91-98. doi: 10.5125/jkaoms.2021.47.2.91. PMID 33911041
• Koc O, Er N, Karaca C, Bilginaylar K. Comparison of the effects of submucosal hyaluronidase and dexamethasone on postoperative edema, pain, trismus, and infection following impacted third molar surgery. BMC Oral Health. 2024 Aug 30;24(1):1018. doi: 10.1186/s12903-024-04729-1. PMID 39215323
• Wang Q, Jin Q, Cai L, Zhao C, Feng P, Jia J, Xu W, Qian Q, Ding Z, Xu J, Gu C, Zhang S, Shi H, Ma H, Deng Y, Zhang T, Song Y, Wang Q, Zhang Y, Zhou X, Pei L, Yang Y, Liang J, Jiang T, Li H, Liu H, Wu L, Kang P. Efficacy of Diosmin in Reducing Lower-Extremity Swelling and Pain After Total Knee Arthroplasty: A Randomized, Controlled Multicenter Trial. J Bone Joint Surg Am. 2024 Mar 20;106(6):492-500 PMID 38109425

Идентификаторы

NCT: NCT07705165 · XC26MIDI0010 · KCT0011945

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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