CClinicalTrials.gg
CompletedNCT03459365Updated Sep 4, 2024Results posted

Euflexxa for the Treatment of Osteoarthritis

An interventional study of Euflexxa in Osteo Arthritis Knee, sponsored by The Cleveland Clinic. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-04.

Sponsored by The Cleveland Clinic · Not applicable, Interventional, and Treatment

Phase
Not applicable
Study type
Interventional
Enrollment
30
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

The effect of Euflexxa therapy for knee osteoarthritis on levels of inflammatory and degenerative synovial fluid bio-markers in patients with knee osteoarthritis

Read the 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.

02

Conditions studied

  • Osteo Arthritis Knee
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

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
04

Study design

Phase
Not applicable
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Euflexxa

    Two sets of Euflexxa injection at 0 and 6 months. Each set consists of 3 injections 1 week apart.

    Device: Euflexxa

Interventions

  • DeviceEuflexxa

    Aspirations performed before each injection and at six weeks.

05

What researchers measure

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

06

Results

Posted Sep 4, 2024

Participant flow

Participant flow — Overall Study
MilestoneEuflexxa
Started24
Completed10
Not completed14
Withdrew: Withdrawal by subject6
Withdrew: Protocol violation8

Outcome measures

PrimaryChange 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
Reported as:
Mean · mg/ml
Change in Hyaluronate Concentration
mg/mlEuflexxa
Change in Hyaluronate Concentration0.29568 ± 1.65476
SecondaryChanges 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
Reported as:
Mean · ng/ml
Changes in Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)
ng/mlEuflexxa
Changes in Tumor Necrosis Factor-stimulated Gene 6 (TSG-6)3450 ± 5831
SecondaryVAS 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
Reported as:
Mean · mm
VAS Pain Score Improvement
mmEuflexxa
VAS Pain Score Improvement40 ± 13

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Euflexxa0/10 (0%)1/10 (10%)0/10 (0%)
Most frequent serious events
Most frequent serious events
EventEuflexxa
Colorectal cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/10

Baseline characteristics

10 patients (11 knees). Baseline description is at the patient level (n=10)

Age, Continuous
Age, Continuous(years)Euflexxa
Mean52 ± 11
Sex: Female, Male
Sex: Female, Male(Participants)Euflexxa
Female6
Male4
Race and Ethnicity Not Collected
Race and Ethnicity Not Collected(Participants)Euflexxa
Body mass index, continuous
Body mass index, continuous(kg/m^2)Euflexxa
Mean30 ± 7
07

Study locations

1 site
  • Cleveland Clinic
    Cleveland, Ohio 44195, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Dec 11, 2017
  • Informed consent form · Sep 12, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No — undecided

09

Registry details

Key details

Study ID
NCT03459365
Lead sponsor
The Cleveland Clinic
Responsible party
Carlos Higuera-Rueda (Vice Chair for Quality and Patient Safety, The Cleveland Clinic) — Principal investigator
First posted
Mar 8, 2018
Start date
Jul 9, 2018
Primary completion
Sep 30, 2021
Completion
Oct 31, 2021
Results posted
Sep 4, 2024
Last update
Sep 4, 2024

Study contacts

Carlos A Higuera, MD
principal investigator · The Cleveland Clinic

Oversight

FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion