Osteo Arthritis Knee
Conditions
Brief summary
The effect of Euflexxa therapy for knee osteoarthritis on levels of inflammatory and degenerative synovial fluid bio-markers in patients with knee osteoarthritis
Detailed description
The FLEXX trial was the first well-controlled, randomized, double-blind, multicenter study evaluating the efficacy of Euflexxa (1% sodium hyaluronate) therapy for knee osteoarthritis. Five-hundred-and-eighty patients were randomized to receive either Euflexxa or normal saline. There were significant improvements in the Visual analogue scale score Osteoarthritis Research Society International responder index, HRQoL, and function at 26-week follow-up.1 However, the FLEXX trial did not evaluate changes in synovial fluid bio-marker levels. The present study will be a prospective pilot study of 30 knees from subjects who receive intra-articular Euflexxa. The primary objective of this study is to prospectively determine, at 6-weeks, and 6-months post treatment, the changes in levels of synovial fluid biomarkers from pre- to post-injection in patients who receive Euflexxa. In addition, we will assess patient reported pain and patient reported outcomes up to 2 years from initiation of study.
Interventions
DEVICEEuflexxa
Aspirations performed before each injection and at six weeks.
Sponsors
The Cleveland Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. OA of the knee by American College of Rheumatology criteria 2. Those who failed non-pharmacological measures or simple analgesics 3. moderate to severe pain score of 41 to 90 mm recorded on 100-mm visual analog scale (VAS) immediately following a 50-foot walk 4. bilateral standing anterior-posterior radiograph demonstrating Kellgren and Lawrence grade 2 or 3 OA of the target knee 5. ability and willingness to use only acetaminophen as the analgesic (rescue) study medication 6. unassisted walking 50 feet on a flat surface and going up and down stairs 7. willingness and ability to complete efficacy and safety questionnaires
Exclusion criteria
1. Age less than 18 years 2. any major injury to the target knee within the prior 12 months 3. any surgery to the target knee within the prior 12 months 4. surgery to the contralateral knee or other weight-bearing 5. inflammatory arthropathies 6. gout or pseudogout within the previous 6 months 7. radiographic acute fracture, severe loss of bone density, avascular necrosis, and/or severe bone or joint deformity in the target knee 8. osteonecrosis of either knee 9. fibromyalgia, pes anserine bursitis, lumbar radiculopathy, and/or neurogenic or vascular claudication 10. target knee joint infection or skin disorder/ infection within the previous 6 months 11. symptomatic OA of the hips, spine, or ankle; known hypersensitivity to acetaminophen, IA-BioHA, or phosphate-buffered saline solution 12. Women of childbearing potential who are pregnant, nursing, or planning to become pregnant, and those who do not agree to remain on an acceptable method of birth control throughout the study 13. history of immune disorders; vascular insufficiency of lower limbs or peripheral neuropathy 14. current treatment or treatment of cancer within the previous 2 years (excluding basal cell or squamous cell carcinoma of the skin) 15. active liver or renal disease 16. any clinically significant abnormal laboratory value \[to be defined in detail at a later point\] 17. any intercurrent chronic disease or condition that might interfere with the completion of the study 18. participation in any experimental device study within the prior 6 months or any experimental drug study within the prior month
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hyaluronate Concentration | Baseline to 6 months | The concentration of hyaluronate in the synovial fluid will be measured using Fluorophore-assisted carbohydrate electrophoresis. The difference between the mean concentration at baseline and 6 months is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Tumor Necrosis Factor-stimulated Gene 6 (TSG-6) | Baseline to 6 months | The levels of TSG-6 in the synovial fluid will be measured using Enzyme-linked immunosorbent assay. The difference in mean concentration between baseline and 6 months post injection is reported. |
| VAS Pain Score Improvement | Baseline to 6 months | Change in VAS (visual analogue scale) pain score compared to baseline in the study cohort. VAS is a measure of pain with 0 being best and 10 being worst pain on a 10 cm scale (100 mm). |
Countries
United States
Participant flow
Pre-assignment details
There were 30 knees (from 24 patients) recruited (some patients treated on both knees). 7 knees withdrew from the study. 8 knees had dry taps. This left 15 knees from 11 patients with adequate baseline aspirates. One of the 1-month aspirates was too bloody to process, leaving 14 knees from 10 patients with adequate baseline and 1 month samples. 3 knees had dry taps at 6 months, leaving 11 knees from 10 patients with adequate baseline, 1 month, and 6 month aspirates for data analysis.
Participants by arm
| Arm | Count |
|---|---|
| Euflexxa Two sets of Euflexxa injection at 0 and 6 months. Each set consists of 3 injections 1 week apart.
Euflexxa: Aspirations performed before each injection and at six weeks. | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 8 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Euflexxa | — |
|---|---|---|
| Age, Continuous | 52 years STANDARD_DEVIATION 11 | — |
| Body mass index, continuous | 30 kg/m^2 STANDARD_DEVIATION 7 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 6 Participants | — |
| Sex: Female, Male Male | 4 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 0 / 10 |
| serious Total, serious adverse events | 1 / 10 |
Outcome results
Primary
Change in Hyaluronate Concentration
The concentration of hyaluronate in the synovial fluid will be measured using Fluorophore-assisted carbohydrate electrophoresis. The difference between the mean concentration at baseline and 6 months is reported.
Time frame: Baseline to 6 months
Population: 11 knees from 10 patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Euflexxa | Change in Hyaluronate Concentration | 0.29568 mg/ml | Standard Deviation 1.65476 |
Secondary
Changes in Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)
The levels of TSG-6 in the synovial fluid will be measured using Enzyme-linked immunosorbent assay. The difference in mean concentration between baseline and 6 months post injection is reported.
Time frame: Baseline to 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Euflexxa | Changes in Tumor Necrosis Factor-stimulated Gene 6 (TSG-6) | 3450 ng/ml | Standard Deviation 5831 |
Secondary
VAS Pain Score Improvement
Change in VAS (visual analogue scale) pain score compared to baseline in the study cohort. VAS is a measure of pain with 0 being best and 10 being worst pain on a 10 cm scale (100 mm).
Time frame: Baseline to 6 months
Population: 11 knees (10 patients)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Euflexxa | VAS Pain Score Improvement | 40 mm | Standard Deviation 13 |