Early Viscosupplementation After ACL Reconstruction: a Randomized Controlled Trial

Study Overview
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Brief Summary
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The possibility of using an intra-articular agent such as hyaluronic acid (HA) to reduce the post-operative inflammatory stress on the knee joint, limiting the use of other pain-killers and promoting a faster recovery after ACL reconstruction, seems attractive. The aim of the present double blind, placebo controlled study is to evaluate the effects, both in terms of pain control and functional recovery, provided by a single HA injection performed in the early postoperative phase after ACL reconstruction. The day after the ACL reconstruction (which is performed with the same technique for all the patients enrolled), the patients were randomized to receive a single injection of HA or 3 ml of saline solution. The randomization list was kept in a dedicated office and the injecting physician contacted it to know the treatment allocation just before the injection, that was performed by a lateral parapatellar approach, after removing the drainages and after attempting aspiration to evacuate any eventual residual blood from the joint. In order to maintain the patient blind to the treatment, a surgical drape was placed to prevent him to see the injective procedure. All patients will be evaluated at 15, 30, 60, 180 and 360 days after surgery by using the following tools: SF-36, IKDC subjective, VAS for pain, EQ-VAS for general Health Status and Tegner score. Also the trans-patellar circumference and active and passive ROM of both knees were registered at each follow-up evaluation.

Detailed Description
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Viscosupplementation is an injective approach used in the orthopaedic practice to manage chondropathy and osteoarthritis (OA) in different joints. In the last decades, several products have been developed by biomedical industries, with different biochemical and physical properties, with the aim of providing the best and long-lasting beneficial effects in OA patients. The rational supporting the use of viscosupplementation is due both to its biomechanical and biological actions. First of all, hyaluronic acid (HA) exerts a lubricant effect improving the rheological properties of synovial fluid thus reducing the mechanical stresses within the joint that are responsible for the activation of nociceptors and further cartilage surface wear. Furthermore, HA binds to cellular receptors and further stimulates endogenous production of hyaluronan, other extracellular matrix components, and it also counteracts inflammatory molecules and proteases that are overexpressed in a diseased joint . In light of these features, HA could be considered an intra-articular drug which can act both as a pain killer and joint regulator agent. These properties could be theoretically exploited also for different clinical applications than a chronic disease like OA. In particular, viscosupplementation might play a beneficial role in restoring the overall joint homeostasis and might contribute to reduce pro-inflammatory stimuli after knee surgical procedures, thus reducing pain and accelerating functional recovery. Anterior cruciate ligament (ACL) reconstruction is one of the most common procedures in the field of sports medicine . It is common for patients to experience persistent knee swelling after the surgical procedure, and this increases pain and delays the start of the rehabilitation program, thus prolonging the times of full functional recovery. The possibility of using an intra-articular agent such as HA to reduce the post-operative inflammatory stress on the knee, limiting the use of other pain-killers and promoting a faster recovery after ACL reconstruction, seems therefore attractive. The aim of the present double blind, placebo controlled randomized study is to evaluate the effects, both in terms of pain control and functional recovery, provided by a single HA injection performed in the early postoperative phase after ACL reconstruction. The day after the ACL reconstruction (which is performed with the same technique for all the subjects enrolled), the patients were randomized to receive a single injection of HA or 3 ml of saline solution. The randomization list was kept in a dedicated office and the injecting physician contacted this office to know the treatment allocation just before the injection, that was performed by a lateral parapatellar approach, after removing the drainages and after attempting aspiration to evacuate any eventual residual blood from the joint. In order to maintain the patient blind to the treatment, a surgical drape was placed to prevent him to see the injective procedure. All patients will be evaluated at 15, 30, 60, 180 and 360 days after surgery by using the following tools: SF-36, IKDC subjective, VAS for pain, EQ-VAS for general Health Status and Tegner score. Also the trans-patellar circumference and active and passive ROM of both knees were registered at each follow-up evaluation.

Official Title
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Early Post-op. Viscosupplementation After Primary Anterior Cruciate Ligament (ACL) Reconstruction: a Randomized, Placebo Controlled Trial

Conditions
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Complete Tear, Knee, Anterior Cruciate Ligament

Intervention / Treatment
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* Biological: viscosupplementation
* Other: Placebo group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: chronic and symptomatic ACL tear requiring primary surgical reconstruction; age between 18 and 50 years; Exclusion Criteria: concurrent articular lesion requiring surgical treatment (just isolated partial meniscectomy was permitted) axial mal-alignment in the index limb unhealthy contra-lateral knee (i.e. functional limitation or pain) concurrent rheumatic or metabolic disease alterations in the other joints of the index limb (e.g.: hip or ankle disease) previous ACL reconstruction in the index knee

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: injection of saline VS injection of Hyaluronic acid
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyaluronic acid group<br>Single injection of 3 ml HA (product name: Hymovis, Fidia Spa, Padova, Italy) the day after ACL reconstruction (after drainage removal) | Biological: viscosupplementation<br>* A single 3 ml hyaluronic acid (HA) injection (viscosupplementation) performed the day after ACL reconstruction, after drainage removal<br>|
| Placebo Comparator: Placebo group<br>Single injection of 3 ml saline solution the day after ACL reconstruction (after drainage removal) | Other: Placebo group<br>* A single 3 ml saline injection performed the day after ACL reconstruction, after drainage removal<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IKDC (International Knee Documentation Committee) Subjective score |  | basal, 6 and 12 months post-op | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Tegner Score |  | basal, 6 and 12 months | 
| Transpatellar circumference trend |  | basal, 15, 30, 60, 180 days post op | 
| Trend in Active and Passive Range of Motion (ROM) of the knee |  | basal, 15, 30, 60, 180 days post op | 
| Change in VAS (Visual Analogue Scale) for general health status |  | basal, 15, 30, 60, 180 days post op | 
| Change in VAS for pain |  | basal, 15, 30, 60, 180 days post op | 
| Change in SF-36 (Short Form Health Survey) Score |  | basal, 6 and 12 months post-op | 
| Adverse events report |  | 15 days | 
| Adverse events report |  | 30 days | 
| Adverse events report |  | 60 days | 
| Adverse events report |  | 180 days |