Intra-articular sodium hyaluronate 2 mL versus physiological saline 20 mL versus physiological saline 2 mL for painful knee osteoarthritis: a randomized clinical trial.
OBJECTIVE
Methodological constraints weaken previous evidence on intra-articular viscosupplementation and physiological saline distention for osteoarthritis. We conducted a randomized, patient- and observer-blind trial to evaluate these interventions in patients with painful knee osteoarthritis.


METHODS
We centrally randomized 251 patients with knee osteoarthritis to four weekly intra-articular injections of sodium hyaluronate 2 mL (Hyalgan 10.3 mg/mL) versus physiological saline 20 mL (distention) versus physiological saline 2 mL (placebo) and followed patients for 26 weeks. Inclusion criteria were age over 59 years and daily knee pain more than 20 mm on a 100-mm visual analogue scale (VAS) without satisfactory response to analgesics. During the trial, rescue analgesic were allowed. The primary outcome was pain on movement. The secondary outcomes were pain at rest, pain during the night, Knee Injury and Osteoarthritis Outcome Score (KOOS), Osteoarthritis Research Society International (OARSI) criteria, and global assessment of the patient's condition.


RESULTS
The mean age of the patients was 69.4 years; 55% were women. The effects of hyaluronate 2 mL, physiological saline 20 mL, and physiological saline 2 mL did not differ significantly in reducing knee pain, knee function, or consumption of analgesics. Using OARSI criteria, no significant differences were found. The VAS and KOOS outcomes all improved significantly over time (p<0.0005), regardless of intervention group. No adverse events were reported.


CONCLUSIONS
Intra-articular hyaluronate or distention with physiological saline did not significantly reduce pain compared with physiological saline placebo in patients with osteoarthritis of the knee.
Lundsgaard
C
C
Department of Geriatrics and Rheumatology, Glostrup Hospital the county of Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark. c.lundsgaard@dadlnet.dk
Dufour
N
N
Fallentin
E
E
Winkel
P
P
Gluud
C
C
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement; D012720:Severity of Illness Index; D016037:Single-Blind Method; D012965:Sodium Chloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D012965:Sodium Chloride; D006820:Hyaluronic Acid