Table 1.
Details of clinical trials in humans
| Study | No. of patients in IA-HA | No. of patients in IA-HA + AI | Age (mean ± SD), years | Stage of OAa | Blinded experiment | Treatments | Outcome extracted | HA characteristics | Results |
|---|---|---|---|---|---|---|---|---|---|
| Grecomoro et al., 1992 [31] | 20 | 20 | 42.3 ± 9.87 | – | – | 1. HA 20 mg, 5 weekly IA 2. DEX 0.4 mg at 1st IA followed by HA for 4 weekly IA |
VAS | HA (MW 500–750 kDa) | • For IA-HA + DEX, pain intensity decreased more rapidly and had lower levels than IA-HA |
| Ozturk et al., 2006 [33] | 24 | 16 | HA, 58 ± 7.7 HA + TA, 58.06 ± 10.3 |
Grade 2–3 [65] | Single-blind | 1. HA 30 mg, 3 weekly IA in 1st month and 3 IA in 6th month 2. TA 10 mg, prior to 1st and 4th IA of HA (at the same condition of HA injection above) |
VAS, WOMAC pain | HA (MW 1000–2900 kDa) | • VAS and WOMAC pain scores were significantly reduced for IA-HA + TA • No significant differences in AE were reported between groups |
| Lee et al., 2011 [32] | 22 | 21 | HA, 69.1 ± 5.1 HA + KE, 61.1 ± 6.6 |
Grade 2–3 [65] | Single-blind | 1. HA 25 mg, 5 weekly IA 2. KE 30 mg, 3 weekly IA, followed by HA, 2 weekly IA |
VAS | HA (MW 940–1020 kDa) | • IA-HA + KE significantly improved pain compared with IA-HA alone • 5 of 21 patients had focal post-injection knee pain 8 h after IA |
| de Campos et al., 2013 [30] | 52 | 52 | HA, 61 ± 12 HA + TH, 65 ± 9 |
Grade 1–4 [66] | Double-blind | 1. HA 48 mg, single IA 2. HA 48 mg and TH 20 mg, single IA |
VAS, WOMAC pain | HA (MW 6000 kDa) | • At week 1, VAS and WOMAC pain scores were lower for IA-HA + TH when compared with IA-HA • There were no differences between groups at weeks 4, 12 and 24 • AE in each group were not different |
| Petrella et al., 2015 [34] | 32 | 34 | HA, 59 ± 12 HA + TA, 61 ± 11 |
Grade 2–3 [65] | Double-blind | 1. HA (Hydros) 6 mL, single IA 2. TA 10 mg + HA (hydros) 6 mL, single IA |
WOMAC pain | Hydros (modified HA polymer with a polyethylene glycol cross-linker which has the ability to entrap a low-dose corticosteroid) | • WOMAC pain scores were reduced in each group over 26 weeks • AE were similar in both treatment groups |
aClassified by Kellgren & Lawrence grading system [65, 66]; −, no details
AE adverse events, DEX dexamethasone, HA hyaluronic acid, IA intra-articular injection, KE ketorolac, kDa kilodaltons, MW molecular weight, OA osteoarthritis, TA triamcinolone acetonide, TH triamcinolone hexacetonide, VAS visual analog scale, WOMAC Western Ontario and McMaster Universities Osteoarthritis Index