| Methods |
Randomised
Controlled
Trial
Single‐blind
(Blinded evaluator)
Parallel‐group
Multicentre (n=14)
ITT analysis n=215,
Safety analysis n=216,
Valid for efficacy n=177 |
| Participants |
Country:
United States
Mean age: 63
% Female: 57
Mean disease duration: NR
Duration: 26 wk
Number randomised: 218
(HA 113, TH 105)
Inclusion:
ambulatory males and females
>= 40 yrs of age
in generally good health
diagnosed with knee OA (ACR criteria) at least 3 mth prior to study entry, required to have been taking analgesics/
NSAIDs to control knee pain at least 3 days/wk for a minimum of 2 mth before study entry
score >= 2 on Q1 of WOMAC Pain subscale at screening,
score of 50‐90/100 mm VAS on both pt and investigator overall assessment,
females of child‐
bearing potential required to use adequate means of contraception.
Exclusion:
any unstable medical condition,
acute synovitis, allergy to avian products/hyaluronan‐based injection components/corticosteroid injections/acetaminophen, inflamatory arthropathy or infection in the area of the injection site, a clinical diagnosis of primarily patello‐
femoral knee pain,
effusion of >10 ml at screening or baseline,
venous or lymphatic statis in the leg,
claudication or peripheral vascular disease, malignancy within 5 y, diabetic neuropathy or related infections, laboratory abnormalities
use of glucosamine and/or chondroitin sulfate prohibited,
exposure to prior viscosupplementation in target knee,
oral corticosteroids or IA corticosteroid injection of a target knee within 3 mth of screening or a nontarget joint within 4 wk,
pts with a history of target joint arthroplasty
Baseline values:
WOMAC Pain Ql:
HA: 2.12
TH: 2.15
Pt VAS score:
HA: 68.4
TH: 67.3
Iv VAS score:
HA: 69.0
TH: 69.6
WOMAC Pain:
HA: 10.7
TH: 10.4
WOMAC Stiffness:
HA: 4.7
TH: 4.9
WOMAC Function
HA: 38.6
TH: 37.9
WOMAC Total:
HA: 54.0
TH: 53.1
% pt analgesics:
HA: 98.2
TH: 97.1 |
| Interventions |
Hylan G‐F 20
(Synvisc) three weekly injections.
Triamcinolone hexacetonide (Aristospan) a single ia injection of 40 mg (2 ml of a 20 mg/ml suspension).
Injection approach not standardised.
18‐22 gauge needle used. Subcutaneous local anaesthetics and anaesthetic skin spray were permitted.
Concurrent therapy: Medications for preexisting conditions were permitted. Except for within 24 h of study visit, the following oral pain medications were allowed: acetaminophen (up to 4000 mg/day); analgesics or short‐acting NSAID with a washout of at least 24 h (according to product labelling) for pain other than in the target knee, but not for more than 3 consecutive days or 10 days per month, and low dose aspirin (<= 325 mg/day) for antithrombotic prophylaxis.
NSAID with once‐daily dose regimens were prohibited.
Longer‐acting analgesics and NSAID (e.g. rofecoxib) were to be discontinued at least 7 days before baseline and not permitted during the study. |
| Outcomes |
Pain walking on a flat surface (WOMAC Pain Q1), Pt and investigator overall assessments (0‐100 mm VAS)
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
WOMAC total score (0‐96),
WOMAC pain
(0‐20), WOMAC stiffness (0‐8),
WOMAC physical function subscale (0‐68),
use of analgesics, rate of early withdrawals, responder rate (pt improved from baseline by at least one point on WOMAC Q1 at a given visit). |
| Notes |
Jadad's:2/5
R‐1,B‐0,W‐1
If effusion present, aspirated and assessed for infection & crystals.
Fourth author, D. Parenti is Asst. VP of Musculoskeletal Products, McNeil Pharmaceuticals, 5th author, C.W. Murray is Director of Musculoskeletal Products, Wyeth Pharmaceuticals. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment (selection bias) |
Unclear risk |
B ‐ Unclear |
