"Intra-articular Hyaluronic Acid Injection for Accelerating Functional Recovery After Knee Arthroscopy"

"Intra-articular Hyaluronic Acid Injection Significantly Accelerates Functional Recovery After Knee Arthroscopy: A Prospective Randomized Controlled Trial"

This study evaluates the effectiveness of intra-articular hyaluronic acid (HA) viscosupplementation and oral chondroitin sulfate (CS) supplementation, in combination with standard postoperative rehabilitation, on functional recovery, pain reduction, and quality of life following knee arthroscopy for medial meniscus injury. Knee arthroscopy is commonly performed for meniscal tears, but the extensive joint irrigation during the procedure removes naturally occurring synovial fluid, potentially prolonging recovery. Hyaluronic acid is the main component of synovial fluid and plays crucial roles in joint lubrication, shock absorption, and cartilage protection. This prospective, randomized, three-arm controlled trial will enroll approximately 290 patients undergoing arthroscopy for medial meniscus injury. Participants will be randomized into three groups: (1) standard rehabilitation alone (Control), (2) rehabilitation plus oral CS supplementation (1200mg CS and 40mg Vitamin C daily for 12 weeks), or (3) rehabilitation plus two intra-articular HA injections (Biolevox™ HA 2.2%, administered at 2 weeks and 6 weeks post-arthroscopy). The primary outcome is knee function assessed using the Knee Injury and Osteoarthritis Outcome Score (KOOS) at 12 weeks. Secondary outcomes include quality of life (WHOQoL-BREF questionnaire) and safety assessments. The study hypothesis is that viscosupplementation with medium molecular weight HA will result in superior functional outcomes compared with oral supplementation or standard rehabilitation alone.

Study Overview

• Status: Completed
• Conditions: Knee Injuries; Meniscus Lesion; Medial Meniscus Tear
• Intervention / Treatment: Behavioral: Standard Postoperative Rehabilitation Protocol; Dietary supplement: Oral Chondroitin Sulfate (Flextrum); Device: ntra-articular Hyaluronic Acid Injection (Biolevox)

Detailed Description

Knee arthroscopy is the most commonly performed orthopedic procedure. Although it offers advantages over open surgery, including reduced postoperative pain and faster recovery, the procedure inevitably involves extensive joint irrigation which removes naturally occurring synovial fluid. Synovial fluid plays a crucial role in joint lubrication and shock absorption. Its reduction following arthroscopy increases friction between articular surfaces, intensifying pain and potentially prolonging rehabilitation. Recovery typically requires 4-6 weeks, during which patients may experience persistent pain and limited joint function. Viscosupplementation with hyaluronic acid (HA) has emerged as a promising approach to addressing post-arthroscopic joint dysfunction. HA is the main non-protein component of synovial fluid, forming a protective layer on articular cartilage, reducing friction and helping maintain tissue resistance to compressive forces. Beyond mechanical effects, HA provides biological benefits including stimulation of endogenous HA synthesis, reduction of proteoglycan loss, and protection of chondrocytes from apoptosis. Oral chondroitin sulfate (CS) supplementation has also been proposed as an adjunctive therapy, with proposed mechanisms including support for cartilage homeostasis through stimulation of proteoglycan and collagen synthesis.

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Poland
  • Bydgoszcz, Poland
    • Department of Orthopedics Collegium Medicum, Nicolaus Copernicus University
  • Grudziądz, Poland
    • Department of Orthopaedics and Traumatology, Regional Hospita

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Age 18-65 years at time of enrollment

• Scheduled for knee arthroscopy for treatment of medial meniscus injury
• Torn medial meniscus with various morphology confirmed by magnetic resonance imaging (MRI)
• Positive clinical examination findings specific for medial meniscus tear OR mechanical symptoms (locking, catching)
• Failed conservative treatment for at least 3 months including physical therapy and/or anti-inflammatory medications
• Grade 0 or Grade 1 osteoarthritis according to Kellgren-Lawrence radiographic classification scale at baseline visit
• Able and willing to provide written informed consent
• Able to comply with study procedures and attend all follow-up visits
• Willing to adhere to postoperative rehabilitation protocol

Exclusion Criteria:

• Prior surgery on the ipsilateral knee (except previous knee arthroscopy for partial meniscectomy and/or chondroplasty)
• Prior surgery on the contralateral knee (except previous knee arthroscopy for partial meniscectomy and/or chondroplasty)
• Intraoperative diagnosis of anterior cruciate ligament (ACL) injury requiring reconstruction
• History of concomitant knee procedures including: ligamentous repair or reconstruction, high tibial osteotomy, distal femoral osteotomy, hardware removal, irrigation and debridement for infection, microfracture procedures, autologous chondrocyte implantation (ACI), osteochondral autograft transfer (OATS), or osteochondral allograft transfer
• Axial knee deformity (varus or valgus malalignment)
• Radiological signs of knee osteoarthritis Grade 2 or higher on Kellgren-Lawrence scale
• Inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, etc.)
• History of septic arthritis in either knee
• Known hypersensitivity or allergy to hyaluronic acid products, chondroitin sulfate, or any study product components
• Active infection or skin disease at the injection site
• Bleeding disorders or current anticoagulation therapy that cannot be safely interrupted
• Pregnancy or lactation - Current participation in another interventional clinical trial
• Any condition that, in the opinion of the investigator, would compromise the participant's ability to participate in the study or potentially confound study results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control - Standard Rehabilitation; Participants receive standard postoperative rehabilitation protocol over 12 weeks consisting of four sequential phases: Phase I (weeks 0-3) - joint protection, partial weight-bearing with brace and crutches, swelling management, patellar mobilization, knee ROM exercises 0-90°, quadriceps isometric exercises, straight-leg raises; Phase II (weeks 3-6) - partial weight-bearing continuation, progressive ROM restoration using stationary bicycle, calf strengthening, balance training; Phase III (weeks 6-9) - full weight-bearing progression once adequate quadriceps control achieved, progressive strengthening exercises (partial squats 0-60° knee flexion, hamstring strengthening), cardiovascular conditioning; Phase IV (weeks 9-12) - advanced functional strengthening including lunges, step-based exercises, single-leg progressions.	Behavioral: Standard Postoperative Rehabilitation Protocol; Evidence-based 12-week progressive rehabilitation program consisting of four phases progressing from joint protection through functional strengthening, including partial/full weight-bearing progression, ROM exercises, quadriceps/hamstring strengthening, balance training, and functional exercises. Arm Group Labels: Control - Standard Rehabilitation; Oral Chondroitin Sulfate Supplementation; Intra-articular Hyaluronic Acid Viscosupplementation
Experimental: Oral Chondroitin Sulfate Supplementation; Participants receive standard postoperative rehabilitation protocol (identical to Control arm) PLUS oral chondroitin sulfate supplementation (Flextrum: 1200mg chondroitin sulfate and 40mg Vitamin C) taken daily for 12 weeks.	Behavioral: Standard Postoperative Rehabilitation Protocol; Evidence-based 12-week progressive rehabilitation program consisting of four phases progressing from joint protection through functional strengthening, including partial/full weight-bearing progression, ROM exercises, quadriceps/hamstring strengthening, balance training, and functional exercises. Arm Group Labels: Control - Standard Rehabilitation; Oral Chondroitin Sulfate Supplementation; Intra-articular Hyaluronic Acid Viscosupplementation; Dietary supplement: Oral Chondroitin Sulfate (Flextrum); Flextrum tablets containing 1200mg chondroitin sulfate and 40mg Vitamin C taken orally once daily for 12 weeks starting immediately post-arthroscopy. Arm Group Labels: Oral Chondroitin Sulfate Supplementation
Experimental: Intra-articular Hyaluronic Acid Viscosupplementation; Participants receive standard postoperative rehabilitation protocol (identical to Control arm) PLUS two intra-articular hyaluronic acid injections (Biolevox™ HA 2.2%, concentration 22mg/mL, volume 2mL, molecular weight 1400-2400 kDa) administered at 2 weeks and 6 weeks post-arthroscopy. Injections are performed under real-time ultrasound guidance using a lateral mid-patellar portal with the knee in full extension, administered by a single certified orthopedic physician.	Behavioral: Standard Postoperative Rehabilitation Protocol; Evidence-based 12-week progressive rehabilitation program consisting of four phases progressing from joint protection through functional strengthening, including partial/full weight-bearing progression, ROM exercises, quadriceps/hamstring strengthening, balance training, and functional exercises. Arm Group Labels: Control - Standard Rehabilitation; Oral Chondroitin Sulfate Supplementation; Intra-articular Hyaluronic Acid Viscosupplementation; Device: ntra-articular Hyaluronic Acid Injection (Biolevox); Biolevox™ HA 2.2% (concentration 22mg/mL, volume 2mL per injection, molecular weight 1400-2400 kDa, bacterial fermentation origin) administered via ultrasound-guided intra-articular injection using lateral mid-patellar approach with knee in full extension. Two injections total: first at 2 weeks post-arthroscopy and second at 6 weeks post-arthroscopy. Manufacturer: Biovico Sp. z o.o., Gdynia, Poland Arm Group Labels: Intra-articular Hyaluronic Acid Viscosupplementation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) Total Score	The KOOS is a validated 42-item patient-reported outcome measure evaluating five domains: Pain (9 items), Other Symptoms (7 items), Function in Daily Living (17 items), Function in Sport and Recreation (5 items), and Knee-related Quality of Life (4 items). Each item is scored on a 0-4 Likert scale. Scores are transformed to 0-100 scale, where 0 represents extreme knee problems, and 100 represents no knee problems. The KOOS Total Score is calculated as the average of all five domain scores. Higher scores indicate better outcomes.	Baseline (pre-surgery) and 12 weeks post-arthroscopy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in KOOS Pain Subscale Score	The KOOS Pain subscale consists of 9 items assessing pain frequency and severity during various activities. Scores range from 0 (extreme pain) to 100 (no pain). Higher scores indicate less pain and better outcomes.	Baseline (pre-surgery) and 12 weeks post-arthroscopy
Change in World Health Organization Quality of Life-BREF (WHOQoL-BREF) - Physical Health Domain	The WHOQoL-BREF is a 26-item questionnaire evaluating health-related quality of life. The Physical Health domain assesses activities of daily living, dependence on medications or medical aids, energy and fatigue, mobility, pain and discomfort, sleep and rest, and work capacity. Domain scores are transformed to a 0-100 scale, where higher scores indicate better quality of life.	Baseline (pre-surgery) and 12 weeks post-arthroscopy
Change in WHOQoL-BREF - Social Relationships Domain	The Social Relationships domain of WHOQoL-BREF assesses personal relationships, social support, and sexual activity. Scores transformed to a 0-100 scale, where higher scores indicate better social relationships.	Baseline (pre-surgery) and 12 weeks post-arthroscopy
Change in WHOQoL-BREF - Environment Domain	The Environment domain of WHOQoL-BREF assesses financial resources, freedom/physical safety/security, health and social care accessibility and quality, home environment, opportunities for acquiring information and skills, participation in and opportunities for recreation/leisure activities, physical environment, and transport. Scores transformed to 0-100 scale where higher scores indicate better environmental quality of life.	Baseline (pre-surgery) and 12 weeks post-arthroscopy
Incidence of Adverse Events	Number of participants experiencing any adverse events, including but not limited to: infection, joint effusion, allergic reactions, injection-site complications, gastrointestinal symptoms, or any other treatment-related adverse effects. Safety will be assessed through participant self-report and clinical examination.	Throughout the 12-week study period
Incidence of Serious Adverse Events	Number of participants experiencing serious adverse events (SAEs) defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.	Throughout 12-week study period

Collaborators and Investigators

• Sponsor: Collegium Medicum w Bydgoszczy
• Investigators: Principal Investigator: Maria Zabrzyńska, MD PhD, Department of Family Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2019
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): March 31, 2022

Study Registration Dates

• First Submitted: March 12, 2026
• First Submitted That Met QC Criteria: March 12, 2026
• First Posted (Actual): March 17, 2026

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 12, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Leg Injuries; Knee Injuries; Carbohydrates; Glycosaminoglycans; Polysaccharides; Chondroitin; Chondroitin Sulfates
• Other Study ID Numbers: 1.0 10.10.2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No