Single intra-articular injection of lightly cross-linked hyaluronic acid reduces knee pain in symptomatic knee osteoarthritis: a multicenter, double-blind, randomized, placebo-controlled trial

  • Stephanie C. Petterson
  • Kevin D. PlancherEmail author



The primary objective was to demonstrate the safety and effectiveness of Monovisc™ in the relief of joint pain in patients with idiopathic knee OA compared to saline injection. It was hypothesized that patient success, defined as ≥ 50% improvement from baseline and ≥ 20 mm absolute improvement from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) visual analog scale (VAS) pain score, would be greater in the Monovisc™ group compared to the Saline control group.


In this multicenter, double-blind, randomized, placebo-controlled trial, patients with idiopathic, symptomatic, knee OA were randomized to either 4 ml single injection of Monovisc™ or 4 ml injection of 0.9% saline. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess patient outcomes at 2, 4, 8, 12, 20, and 26 weeks post-injection. The primary effectiveness endpoint was a 50% improvement and ≥ 20 mm improvement from baseline in the WOMAC pain through 26 weeks. Secondary outcome measures included a ≥ 20 mm improvement from baseline on the WOMAC physical function, patient global assessment, evaluator global assessment, and knee range of motion.


369 patients (154 male, 215 female) were randomized to either Monovisc™ or saline. The Monovisc™ group had a significantly greater rate of patient success (e.g. ≥ 50% improvement and ≥ 20 mm absolute improvement from baseline in the WOMAC pain through Week 26) compared to saline (p = 0.043).


Monovisc™, a single-injection intra-articular HA device, is a safe and effective treatment for providing a clinically meaningful reduction in knee pain within 2 weeks. The results of this study support the use of a single injection of hyaluronic acid (Monovisc™) for patients with symptomatic knee OA in patients older than 45 years, as a safe and effective alternative for patients who may want an alternative treatment modality or may not be candidates for partial or total knee replacement.

Level of evidence

I, multicenter, double-blind, randomized, placebo-controlled trial.


Monovisc™ Hyaluronic acid Knee osteoarthritis Intra-articular injection Knee joint pain 





Western Ontario and McMaster Universities Osteoarthritis Index


Visual analog scale


United States


Non-steroidal anti-inflammatory medications


Hyaluronic acid


United States dollar


American Academy of Orthopaedics


Institutional Review Board


Good clinical practice


International Conference on Harmonization


Body mass index




Medical Dictionary for Regulatory Activities




Per protocol


Generalized estimating equations


Minimum clinically important differences


Range of motion


American College of Rheumatology


Osteoarthritis Research Society International



The authors would like to personally thank all the principal investigators and study coordinators for their help with subject recruitment and data collection. Special thanks go to Dr. Baraf, Dr. Covall, Dr. Kivitz, and Dr. Neustadt for their assistance in the completion of this manuscript and to Gary Stevens for his assistance with the data analysis.

Author contribution

Drs. Stephanie Petterson and Kevin Plancher were responsible for all aspects of manuscript development and submission.


This manuscript is based upon clinical trial results from a study sponsored by Anika Therapeutics.

Compliance with ethical standards

Conflict of interest

Grants or other financial support were received from Anika Therapeutics.

Ethical approval

Ethics committee approvals were obtained.


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Copyright information

© European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA) 2018

Authors and Affiliations

  1. 1.Orthopaedic FoundationStamfordUSA
  2. 2.Albert Einstein College of Medicine/Montefiore Hospital, Plancher Orthopaedics and Sports MedicineNew YorkUSA

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