Osteoarthritis
Conditions
Keywords
Hyaluronan, Carpometacarpal, Outcomes, Carpometacarpal Joints
Brief summary
Hyaluronan is a man-made preparation of a protein complex that occurs naturally in joints and that is often low in people with osteoarthritis. Although hyaluronan has been used in millions of people with knee osteoarthritis, it is not yet FDA approved for use in the thumb. The purpose of this study is to determine the safety and effectiveness of hyaluronan in relieving arthritis symptoms at the base of the thumb and to compare it to corticosteroids and local anesthetic. The principle hypothesis is that treating osteoarthritis at the carpometacarpophalangeal (CMC) joint with injectable hyaluronan will results in greater pain relief, higher patient satisfaction, and better functional outcomes than treating with placebo injections (local anesthetic) or with corticosteroid injections. Treating CMC osteoarthritis with corticosteroid injections will result in greater pain relief, higher patient satisfaction, and better functional outcomes than treating with placebo injections. Patients with worse pre-treatment function will have less improvement and worse post-treatment results after administration of corticosteroid or hyaluronan.
Detailed description
Osteoarthritis involves a wearing down of the cartilage within a joint. It can affect any joint in the body, but it most commonly affects joints in the hands, hips, knees, and spine. Over the last few years, a new medicine called hyaluronan has been used for treating osteoarthritis. Hyaluronan is a man-made preparation of a protein complex that occurs naturally in joints and that is often low in people with osteoarthritis. Although hyaluronan has been used in millions of people with knee osteoarthritis, it is not yet FDA approved for use in the thumb. The purpose of this study is to determine the safety and effectiveness of hyaluronan in relieving arthritis symptoms at the base of the thumb and to compare it to corticosteroids and local anesthetic. Specifically, the study will evaluate pain relief, patient satisfaction, and functional outcomes among participants. Participation in this study will last 26 weeks. Screening will include a questionnaire and an x-ray of the affected thumb. Eligible participants will then be randomly assigned to one of three treatments: two hyaluronan injections, one corticosteroid injection plus one local anesthetic injection, or two local anesthetic injections. Participants will receive the injections at the base of their thumb, and the first injection will be followed by the second injection a week later. There will be five study visits that will occur at baseline and Weeks 2, 4, 12, and 26. All study visits will include questionnaires, and except for the Week 2 study visit, they will also include an examination and evaluation of the affected thumb. Photographs of the thumb will be taken at baseline. The injections will occur at baseline and Week 2. At Weeks 8 and 20, questionnaires will be mailed to participants for them to complete. Upon completing the study, participants will have the option of receiving continued treatment with another round of hyaluronic injections.
Interventions
DRUGSynvisc (Hylan G-F20; hyaluronan injection)
1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks
DRUGBupivicaine (local anesthesia injection)
1 ml of bupivicaine 0.5% injected once a week for 2 weeks
DRUGKenalog (triamcinolone; corticosteroid injection)
1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation
Sponsors
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Genzyme, a Sanofi Company
Hospital for Special Surgery, New York
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to 95 Years
Healthy volunteers
No
Inclusion criteria
* Presence of osteophytes or sclerosis at the carpometacarpal (CMC) joint * Complaint of unacceptable pain despite modification of activity and a therapeutic dose of nonsteroidal anti-inflammatory drugs (NSAIDS), if tolerated * If bilateral disease, only the most severely involved hand (as defined by the visual analog scale \[VAS\] for pain) will be entered in the study * Able to follow instructions and complete questionnaires * Failed conservative therapy with NSAIDS or COX-2 inhibitors * Unable to tolerate COX-2 inhibitors
Exclusion criteria
* Previous traumatic dislocation, ligament tear, or fracture of the thumb in the affected hand * Previous hand surgery on the affected hand * Known hand comorbidities (e.g., active carpal tunnel syndrome, de Quervains tenosynovitis, etc.) * Systemic rheumatic disease * Bleeding diatheses or anti-coagulation * Allergies to steroids, chicken products, bupivicaine, or adhesive (e.g., double-sided tape) * Current use of oral or intravenous steroids * Active systemic malignancies * Hyaluronan injection in the target CMC joint in the last 6 months * Steroid or hyaluronan injection in any other joint in the last 6 months * Insulin dependent diabetes mellitus (IDDM) * Active infection * Pain in the index joint that is more than 40 out of 100 on a VAS Pain scale * End Stage CMC osteoarthritis, equivalent to bone on bone, Kellgren and Lawrence Stage IV * Grade 3 or 4 Eaton and Litter (E+L) Classification * E+L 3: Advanced joint distraction, subchondral cysts, and sclerosis * E+L 4: Involvement of several joint surfaces
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Visual Analogue Scale (VAS) | Baseline, 26 Weeks | Pain intensity measured on a Visual Analog Scale with scores ranging from 0 to 100, with 100 = severe pain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire | Baseline, 26 Weeks | Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire measures degree of disability on a scale of 0 to 100, with a higher score indicating greater disability. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from the practices of Hospital for Special Surgery (HSS) physicians or were or self-referred. Study information was posted on the HSS website, clinicaltrials.gov, Craig's List and local newspapers. Recruitment occurred between 05/25/2007 and 07/15/2009.
Pre-assignment details
396 subjects screened 169 did not meet eligibility criteria 27 declined injection 200 subjects randomized
Participants by arm
| Arm | Count |
|---|---|
| Bupivicaine Bupivicaine (local anesthetic)
Bupivicaine (local anesthesia injection): 1 ml of bupivicaine 0.5% injected once a week for 2 weeks | 66 |
| Triamcinolone Corticosteroid (trimcinolone (Kenalog) 40 mg)
Kenalog (triamcinolone; corticosteroid injection): 1 ml (40mg) of triamcinolone (Kenalog) injected the first week, followed by a placebo injection of 1 ml 0.5% bupivacaine the second week; Kenalog is a non-suspension steroid preparation and is less likely to cause post-injection flares than a suspension preparation | 68 |
| Hylan G-F 20 Synvisc
Synvisc (Hylan G-F20; hyaluronan injection): 1 ml of hyaluronan (Synvisc) injected once a week for 2 consecutive weeks | 66 |
| Total | 200 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 7 | 6 | 4 |
| Overall Study | Unable to complete requirements of study | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 1 | 2 |
Baseline characteristics
| Characteristic | Bupivicaine | Triamcinolone | Hylan G-F 20 | Total |
|---|---|---|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 9.3 | 66.6 years STANDARD_DEVIATION 8.4 | 67.1 years STANDARD_DEVIATION 10.1 | 66.7 years STANDARD_DEVIATION 9.3 |
| Race/Ethnicity, Customized Race No data | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Other | 8 Participants | 7 Participants | 4 Participants | 19 Participants |
| Race/Ethnicity, Customized Race White | 58 Participants | 61 Participants | 61 Participants | 180 Participants |
| Sex/Gender, Customized Gender Female | 50 Participants | 40 Participants | 45 Participants | 135 Participants |
| Sex/Gender, Customized Gender Male | 16 Participants | 28 Participants | 20 Participants | 64 Participants |
| Sex/Gender, Customized Gender No data | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 66 | 10 / 68 | 3 / 66 |
| serious Total, serious adverse events | 1 / 66 | 0 / 68 | 2 / 66 |
Outcome results
Primary
Pain Visual Analogue Scale (VAS)
Pain intensity measured on a Visual Analog Scale with scores ranging from 0 to 100, with 100 = severe pain.
Time frame: Baseline, 26 Weeks
Population: Patients who completed follow-up through 26 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bupivicaine | Pain Visual Analogue Scale (VAS) | Pain VAS at Baseline | 57.1 Units on a scale | Standard Deviation 20.1 |
| Bupivicaine | Pain Visual Analogue Scale (VAS) | Pain VAS at 26 weeks | 42.9 Units on a scale | Standard Deviation 26.5 |
| Triamcinolone | Pain Visual Analogue Scale (VAS) | Pain VAS at Baseline | 63.2 Units on a scale | Standard Deviation 20.2 |
| Triamcinolone | Pain Visual Analogue Scale (VAS) | Pain VAS at 26 weeks | 50.1 Units on a scale | Standard Deviation 29.4 |
| Hylan G-F 20 | Pain Visual Analogue Scale (VAS) | Pain VAS at Baseline | 60.7 Units on a scale | Standard Deviation 19.3 |
| Hylan G-F 20 | Pain Visual Analogue Scale (VAS) | Pain VAS at 26 weeks | 49.8 Units on a scale | Standard Deviation 26.3 |
Secondary
Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire
Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire measures degree of disability on a scale of 0 to 100, with a higher score indicating greater disability.
Time frame: Baseline, 26 Weeks
Population: Patients who completed follow-up through 26 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Bupivicaine | Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire | DASH at Baseline | 25.7 units on a scale | Standard Deviation 17.1 |
| Bupivicaine | Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire | Dash at 26 Weeks | 24.2 units on a scale | Standard Deviation 17.4 |
| Triamcinolone | Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire | DASH at Baseline | 28.9 units on a scale | Standard Deviation 17.9 |
| Triamcinolone | Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire | Dash at 26 Weeks | 27.0 units on a scale | Standard Deviation 18 |
| Hylan G-F 20 | Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire | DASH at Baseline | 28.8 units on a scale | Standard Deviation 17.3 |
| Hylan G-F 20 | Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire | Dash at 26 Weeks | 26.1 units on a scale | Standard Deviation 19 |