| Methods |
Randomised
Controlled
Trial
Arthrocentesis controlled
Multicentre n=24, (Canada n=3, USA n=21)
Double‐blind
7‐day washout
NSAID and analgesics
January 2001 to December 2002 |
| Participants |
Country:
Canada and the United States
Mean age: 176.4
% Female: 47.9
Mean disease duration: NR
Duration:28 wk
Number randomised: 372
(O4 128,
O3A1 120, and
A4 124)
Inclusion:
greater than or equal to 40 y of age,
willing to discontinue all analgesics and NSAID 7 days before the first injection and for the duration of the study,
diagnosis of knee OA according to ACR criteria,
Kellgren‐Lawrence grade 1,2 or 3,
a summed WOMAC pain score greater than or equal to 200 mm and less than 400 mm (maximum 500) in the index (treated) knee and less than 150 mm in the contralateral (untreated) knee
Exclusion:
patients who initiated an exercise or physical therapy program within 3 mth,
oral or parenteral corticosteroid use within 30 days,
intraarticular injection of steroids into the index knee within 90 days,
intraarticulr injection of any hyaluronic substanced within the past 9 mth or operative arthroscopy within 6 mth,
treatment with anticoagulants,
clinically significant comorbidity (fibromyalgia, peripheral neuropathy, vascular insufficiency or hemiparesis) severe enough to interferewith accurate evaluation
Baseline values:
(based on evaluable (per protocol) population)
WOMAC pain
index knee
O4: 286.6
O3A1: 289.0
A4: 294.1
contralateral knee
O4: 66.8
O3A1: 69.3
A4: 64.6
Patient global
O4: 67.5
O3A1: 62.4
A4: 64.4
Investigator global
O4: 58.8
O3A1:57.0
A4: 57.6
Pain on standing
O4: 65.2
O3A1: 65.7
A4: 65.5
Synovial fluid volume (ml)
O4: 0.9
O3A1: 1.0
A4: 0.9
Mean analgesic usage (tablets/day):
O4: 2.08
O3A1: 2.48
A4: 2.05 |
| Interventions |
1) O4: Orthovisc 2 ml (30 mg) 4 weekly injections
2) O3A1: Orthovisc 2 ml (30 mg) 3 weekly injections plus one control arthrocentesis procedure
3) A4: 4 control arthrocentesis
All injections were administered by either lateral or medial approach after instillation of 1% lidocaine hydrochloride solution. If fluid present, joint space aspirated to dryness.
Concurrent therapy: Acetaminophen up to 4 g/day allowed but not permitted for at least 24h prior to each study assessment visit.
NSAIDs and other analgesics not permitted during the study. |
| Outcomes |
The proportion of patients achieving a 20% relative and 50 mm absolute improvement from baseline in WOMAC pain score at weeks 8, 12, 16 and 22 post baseline in the Index Knee (0‐500 mm VAS)
‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐
patient global score,
investigator global score and pain on standing score all scored on a 0 to 100 mm VAS |
| Notes |
Jadad's: 5/5
R‐2, B‐2, W‐1
The evaluable poulation (patients who received all 4 treatments and at least one followup visit and who had no significant protocol deviation) was considered the primary planned analysis population NOT the intent to treat population.
Screend patients: 888;
Randomised patients: 372;
ITT (safety) O4: 128, O3A1: 119, A4: 123;
Evaluable: 336
O4: 115, O3A1: 107, A4: 114;
Per protocol: 258
O4: 93, O3A1: 76, A4: 89 |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Allocation concealment (selection bias) |
Low risk |
A ‐ Adequate |
