A Randomized, Split Body, Evaluator-blinded, Trial on the Effect of Tergase Injection (Berahyaluronidase Alfa) on Reducing Edema After Both Total Knee Arthroplasty
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 主要终点
- Percent Change From Baseline in Composite Edema Index Based on Leg Circumference Measurements
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
This study employs an evaluator-blinded design to maintain objectivity. Due to the nature of the intervention (subcutaneous injection), it is physically impossible to blind the injector. Therefore, the study strictly separates the unblinded injector from the blinded evaluator who measures efficacy outcomes. The blinded evaluator is prohibited from attending the injection site and remains unaware of the treatment assignment.
入排标准
- 年龄范围
- 60 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
- •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.
结局指标
主要结局
Percent Change From Baseline in Composite Edema Index Based on Leg Circumference Measurements
时间窗: Baseline, Postoperative Day 2
The Composite Edema Index is calculated as the arithmetic mean of the percent change from preoperative baseline in leg circumference measured at four prespecified anatomical locations: calf at the thickest part, suprapatellar area just above the patella, infrapatellar area just below the patella, and thigh 10 cm above the patella. A higher percentage indicates greater postoperative edema.
次要结局
- Percent Change From Baseline in Mean Leg Circumference Swelling Rate(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(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(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(Baseline, Week 6, and Month 3)
- CT-Measured Mean Lower Extremity Soft Tissue Thickness at Postoperative Day 2(Postoperative Day 2)
- Change From Baseline in Serum C-Reactive Protein Concentration(Baseline, Postoperative Day 1, Week 2, and Month 3)
- Change From Baseline in Serum Amyloid A Concentration(Baseline, Postoperative Day 1, Week 2, and Month 3)
- Number of Participants With at Least One Predefined Postoperative Complication(From immediately after surgery through postoperative Month 3)
- Number of Participants With at Least One Adverse Event(From investigational product administration through postoperative Month 3)
- Number of Participants With Clinically Significant Abnormal Vital Sign Findings(From Screening Visit through postoperative Month 3)
- Number of Participants With Clinically Significant Abnormal Physical Examination Findings(From Screening Visit through postoperative Month 3)
- Number of Participants With Clinically Significant Abnormal Clinical Laboratory Test Results(From Screening Visit through postoperative Month 3)
研究者
Man Soo Kim
Professor
Seoul St. Mary's Hospital