Prediction of Response to Intra-articular Injections of Hyaluronic Acid for Knee Osteoarthritis

The purpose of this study is to evaluate whether the investigators can develop a computer algorithm to predict which individual patients will respond to injections of hyaluronic acid (HA) products for knee osteoarthritis.

Study Overview

• Status: Completed
• Conditions: Osteoarthritis, Knee
• Intervention / Treatment: Device: hylan G-F 20; Device: 1% sodium hyaluronate

Detailed Description

Background Osteoarthritis (OA) of the knee is a debilitating condition that affects an estimated 21 million Americans. This number is expected to rise steadily as the population ages. The medical expenditures associated with arthritis and other rheumatic conditions in the United States have increased from $50 billion in 1997 to $86 billion in 2003. In 2003, almost 420,000 total knee replacements were performed, primarily for arthritis. Injections of hyaluronic acid (HA) have been shown to provide symptom relief for many OA patients who have failed to respond to conservative interventions. Many other patients, however, experience only slight or no improvement. The results from this study will allow physicians to identify whether a patient is likely or not likely to respond well to HA therapy leading to improved treatment success rates.

Goals This study has two related goals: 1) to identify patient and treatment factors that predict response to intra-articular injections of hyaluronic acid for knee osteoarthritis using multivariable analysis and 2) develop mathematical and statistical models that will predict individual patient response to HA for knee OA.

It is anticipated that the investigators will develop computer software in this study that can support clinical decision making related to viscosupplementation in the treatment of knee OA. If this project yields successful patient predictive models, physicians who are considering a trial of HA for a patient will have some empirical basis for treatment selection. Eventually a physician would be able to assess a relatively small number of variables for a patient and then be provided with predictions regarding treatment response.

**Please note that the study site at the Naval Medical Center in Portsmouth, Virginia can only enroll patients who are eligible to be treated at a military facility.

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Portsmouth, Virginia, United States, 23708-2197
      • Naval Medical Center Portsmouth (this site can only enroll patients who are eligible to be treated at a military facility)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Symptomatic knee osteoarthritis presenting to physician's office
• Radiographic evidence of knee osteoarthritis
• Age 18 years or older
• Failed minimum of 3 months of non-operative treatment, including, but not limited to, Tylenol, anti-inflammatory medication, cortisone injection, physical therapy, bracing, and/or heel wedge
• Symptoms for at least 3 months

Exclusion Criteria:

• Associated ligamentous instability
• History of deep knee infection
• Candidate for total knee arthroplasty or arthroscopy
• Peripheral neuropathy.
• X-rays that are completely negative and only MRI evidence or arthroscopic evidence (from previous arthroscopy) of OA.
• Prior HA injections at any point in the past
• Chondrocalcinosis
• Patients with precautions or contraindications for viscosupplementation use
• Cortisone injection within past 3 months

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Synvisc (hylan G-F 20)	Device: hylan G-F 20; Three 2 cc injections at weekly intervals; Other Names: Synvisc
Active Comparator: Euflexxa (1% sodium hyaluronate)	Device: 1% sodium hyaluronate; Three 2 cc injections at weekly intervals; Other Names: Euflexxa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Scale	The KOOS is 42-item patient-report questionnaire that assesses symptoms and problems associated with knee injury and osteoarthritis. It yields scores for five scales including Pain, Other Symptoms, Function in Daily Living, Function in Sport/Recreation, and Knee-Related Quality of Life. We used only the Pain scale which has a range of 0 to 100 where 100 represents the "best" score, i.e., no pain. We reported differences in baseline Pain scale score from Pain scale score at 6 months so these scores could theoretically range from -100 (moving from no pain to maximum pain) to 100 (moving from maximum pain to no pain). Positive change scores represent improvement from baseline.	Baseline and at 6 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Analogue Scale (VAS) at 6 Months	The VAS is a patient-reported assessment of knee pain. Patients mark on a line (0-100mm) their current level of knee pain while moving where 0 represent no pain and 100 represents maximum pain. We report changes in VAS pain rating between baseline and 6 month follow-up. Therefore scores can theoretically range from -100 (moving from maximum pain to no pain) to 100 (moving from no pain to maximum pain). Negative change scores represent decreases in perceived pain or improvement.	Assessments were at baseline to 6 month follow-up

Collaborators and Investigators

• Sponsor: American Orthopaedic Society for Sports Medicine
• Collaborators: United States Naval Medical Center, Portsmouth
• Investigators: Study Chair: Robert Marx, MD, Hospital for Special Surgery, New York; Principal Investigator: Marlene DeMaio, MD, United States Naval Medical Center, Portsmouth

Publications and helpful links

Helpful Links

• Information on Osteoarthritis from the National Institutes of Health
• Cochrane Review Article Abstract on Viscosupplementation for Knee Osteoarthritis

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: March 12, 2012
• First Submitted That Met QC Criteria: March 16, 2012
• First Posted (Estimate): March 20, 2012

Study Record Updates

• Last Update Posted (Estimate): April 2, 2014
• Last Update Submitted That Met QC Criteria: February 19, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Osteoarthritis; Osteoarthritis, Knee; Physiological Effects of Drugs; Immunologic Factors; Protective Agents; Adjuvants, Immunologic; Viscosupplements; Hyaluronic Acid; Hylan
• Other Study ID Numbers: AOSSM 51H