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

NCT07705165 | Not Yet Recruiting

• 2 other identifiers: XC26MIDI0010KCT0011945
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Osteoarthritis, Knee; Postoperative Edema; Bilateral Total Knee Arthroplasty

Keywords

Tergase; Berahyaluronidase alfa; Recombinant human hyaluronidase; Total Knee Arthroplasty; Postoperative Edema; Split-body trial

Outcome Measures

Primary Outcomes (1)

• Percent Change From Baseline in Composite Edema Index Based on Leg Circumference Measurements

  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.

  Baseline, Postoperative Day 2

Secondary Outcomes (12)

• 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

Study Arms (2)

Tergase Injection Knee

EXPERIMENTAL

One knee of the subject, randomly assigned to receive a subcutaneous injection of 4,500 IU (3 vials) of Tergase (Berahyaluronidase alfa) at 8 points immediately after total knee arthroplasty (TKA).

Drug: Berahyaluronidase alfa

Untreated Control Knee

NO INTERVENTION

The contralateral knee of the same subject which does not receive any injection, serving as a self-control for efficacy and safety comparisons.

Interventions

Berahyaluronidase alfa DRUG

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.

Also known as: Tergase Inj., Recombinant human hyaluronidase

Tergase Injection Knee

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Man Soo Kim: lead

Related Publications (5)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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. doi: 10.2106/JBJS.23.00854. Epub 2023 Dec 18.

  PMID: 38109425 BACKGROUND

Related Links

• Clinical Research Information Service (CRIS) registration record

MeSH Terms

Conditions

Osteoarthritis, Knee

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This is a randomized, split-body, evaluator-blinded study. Each participant receives the intervention on one randomly assigned knee, while the other knee serves as an untreated control * Intervention Type: Drug * Intervention Name: Tergase Inj. (Berahyaluronidase alfa) * Description: 4,500 IU (3.0 mL) divided into 8 points (approx. 0.375 mL per point) injected subcutaneously around the suture line.

Study Record Dates

• First Submitted: May 14, 2026
• First Posted: July 15, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): March 31, 2028
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share