Clinical trial NCT02630407: Early Viscosupplementation After ACL Reconstruction: a Randomized Controlled Trial
Official title: Early Post-op. Viscosupplementation After Primary Anterior Cruciate Ligament (ACL) Reconstruction: a Randomized, Placebo Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Complete Tear, Knee, Anterior Cruciate Ligament
Lead sponsor: Istituto Ortopedico Rizzoli
Sponsor class: OTHER
First posted: 2015-12-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: injection of saline VS injection of Hyaluronic acid
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in IKDC (International Knee Documentation Committee) Subjective score
timeFrame: basal, 6 and 12 months post-op
Secondary outcomes:
measure: Change in Tegner Score
timeFrame: basal, 6 and 12 months
measure: Transpatellar circumference trend
timeFrame: basal, 15, 30, 60, 180 days post op
measure: Trend in Active and Passive Range of Motion (ROM) of the knee
timeFrame: basal, 15, 30, 60, 180 days post op
measure: Change in VAS (Visual Analogue Scale) for general health status
timeFrame: basal, 15, 30, 60, 180 days post op
measure: Change in VAS for pain
timeFrame: basal, 15, 30, 60, 180 days post op
measure: Change in SF-36 (Short Form Health Survey) Score
timeFrame: basal, 6 and 12 months post-op
measure: Adverse events report
timeFrame: 15 days
measure: Adverse events report
timeFrame: 30 days
measure: Adverse events report
timeFrame: 60 days
measure: Adverse events report
timeFrame: 180 days
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: II Orthopaedic Clinic, Rizzoli Orthopaedic Institute
state: Emilia Romagna
Study officials:
affiliation: II Clinic & Nano-biotechnology Lab, Rizzoli Orthopaedic Institute, Bologna, Italy
name: Elizaveta Kon, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Henrotin Y, Raman R, Richette P, Bard H, Jerosch J, Conrozier T, Chevalier X, Migliore A. Consensus statement on viscosupplementation with hyaluronic acid for the management of osteoarthritis. Semin Arthritis Rheum. 2015 Oct;45(2):140-9. doi: 10.1016/j.semarthrit.2015.04.011. Epub 2015 Apr 30.
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citation: Filardo G, Di Matteo B, Di Martino A, Merli ML, Cenacchi A, Fornasari P, Marcacci M, Kon E. Platelet-Rich Plasma Intra-articular Knee Injections Show No Superiority Versus Viscosupplementation: A Randomized Controlled Trial. Am J Sports Med. 2015 Jul;43(7):1575-82. doi: 10.1177/0363546515582027. Epub 2015 May 7.
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citation: Braithwaite GJ, Daley MJ, Toledo-Velasquez D. Rheological and molecular weight comparisons of approved hyaluronic acid products - preliminary standards for establishing class III medical device equivalence. J Biomater Sci Polym Ed. 2016;27(3):235-46. doi: 10.1080/09205063.2015.1119035. Epub 2015 Dec 31.
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citation: Di Martino A, Tentoni F, Di Matteo B, Cavicchioli A, Lo Presti M, Filardo G, Zaffagnini S, Marcacci M, Kon E. Early Viscosupplementation After Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial. Am J Sports Med. 2016 Oct;44(10):2572-2578. doi: 10.1177/0363546516654909. Epub 2016 Jul 27.