Intraarticular Injection of a Cross-Linked Sodium Hyaluronate Combined with Triamcinolone
Hexacetonide (Cingal) to Provide Symptomatic Relief of Osteoarthritis of the Knee:
A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Trial.
OBJECTIVE: To evaluate the efficacy and safety of an intraarticular injection of Cingal
(Anika Therapeutics, Inc., Bedford, MA) compared with Monovisc (Anika Therapeutics,
Inc., Bedford, MA) or saline for the treatment of knee osteoarthritis. DESIGN: This
multicenter, double-blind, saline-controlled clinical trial randomized subjects with
knee osteoarthritis (Kellgren-Lawrence grades I-III) to a single injection of Cingal
(4 mL, 88 mg hyaluronic acid [HA] plus 18 mg triamcinolone hexacetonide [TH]), Monovisc
(4 mL, 88 mg HA), or saline (4 mL, 0.9%). The primary efficacy outcome was change
in WOMAC (Western Ontario and McMaster Universities Arthritis Index) Pain Score through
12 weeks with Cingal versus saline. Secondary outcomes included Patient and Evaluator
Global Assessments, OMERACT-OARSI Responder index, and WOMAC Total, Stiffness, and
Physical Function scores through 26 weeks. RESULTS: A total of 368 patients were treated
(Cingal, n = 149; Monovisc, n = 150; saline, n = 69). Cingal improvement from baseline
was significantly greater than saline through 12 weeks ( P = 0.0099) and 26 weeks
( P = 0.0072). WOMAC Pain was reduced by 70% at 12 weeks and by 72% at 26 weeks with
Cingal. Significant improvements were found in most secondary endpoints for pain and
function at most time points through 26 weeks. At 1 and 3 weeks, Cingal was significantly
better than Monovisc for most endpoints; Cingal and Monovisc were similar from 6 weeks
through 26 weeks. A low incidence of related adverse events was reported. CONCLUSIONS:
Cingal provides immediate and long-term relief of osteoarthritis-related pain, stiffness,
and function, significant through 26 weeks compared to saline. Cingal had similar
immediate advantages compared with HA alone, while showing benefit comparable to HA
at 6 weeks and beyond.
