Table 3.
Summary table of clinical trials evaluating the efficacy of injectable hybrid cooperative complexes of hyaluronic acid in joint diseases
| Author | Design | Patient characteristics | Intervention | Outcomes | ||||
|---|---|---|---|---|---|---|---|---|
| Joint | No. | Age (mean or range) | Treatment | No. of injections | Follow-up (months) | |||
| High and low molecular weight hyaluronic acid (HA-HL) | ||||||||
| Migliore (2021) [52] | RCT | Knee | 692 | 63.7 |
HA-HL Placebo (saline) |
1 | 6 |
VAS pain rapidly decreased. Pain improvement was significantly in favor of HA-HL at 1, 6, 12, and 24 weeks HA-HL improved functionality, OMERACT-OARSI response and HR-QoL |
| Papalia (2016) [58] | RCT | Knee | 48 | 37.2 (34–39) |
HA-HL PRP |
3 | 12 | Significantly superior clinical and pain outcomes compared with PRP at 3 and 6 months |
| Papalia (2019) [54] | RCT | Knee | 60 | 40–70 |
HA-HL + PRP HA-HL |
3 | 12 | Both improved KOOS and VAS pain. HA-HL + PRP significantly better than HA-HL alone at 3 and 6 months (KOOS) and 3 and 12 months. (VAS) |
| Manciameli (2018) [51] | Prospective | Knee | 35 (59 knees) | 59 | HA-HL | 2 | 6 | VAS pain and WOMAC pain and HR-QoL improved by 1 month and kept stable through 6 months |
| Papalia (2017) [53] | RCT | Knee | 48 obese patients |
61.5 60 |
HA-HL HMW HA |
2 | 6 |
VAS pain, IKDC and KOOS significantly improved at 3 and 6 months in both groups HA-HL was more effective than HMW HA |
| Scaturro (2021) [55] | Prospective | Knee | 37 overweight patients | 63 (45–75) | HA-HL | 2 | 3 | Pain, WOMAC, 6MWT and QoL improved significantly at 3 months |
| Abate (2017) [30] | Prospective/retrospective | Hip | 20 |
63.6 63.3 |
HA-HL HMW HA |
4 | 6 |
VAS pain scores at rest and during activities improved at 3 and 6 months HA-HL significantly better than HMW HA at 6 months |
| La Paglia (2017) [56] | Retrospective | Hip | 32 | 18–55 years |
HA-HL + PRP HMW HA |
2 | 6 | Combined treatment was more effective that HMW HA at 2 and 6 months, particularly in mild-to high grade arthropathy |
| Conforti (2020) [59] | Case series | Shoulder | 97 |
54.3 52.7 |
HA-HL + laser needling ± US-PICT | 2–3 | 3 | VAS pain and ASES improved after treatment and at 3 months in both groups; US-PICT did not significantly improve response |
| Tenti (2017) [42] | Retrospective | Trapezio-metacarpal | 100 |
68.6 65.5 |
HA-HL Triamcinolone acetonide |
2 | 6 |
Both treatments improved VAS pain, FIHOA and HR-QoL HA-HL was significantly superior to triamcinolone at 1 and 6 months |
| Bartolini (2019) [60] | Prospective | Trapezio-metacarpal | 12 | 63 | HA-HL | 2 | 6 | HA-HL reduced VAS pain and improved hand function by 1 month and persisting for 6 months of follow-up |
| Hyaluronic acid plus sodium chondroitin non-sulfated (HA-SC) | ||||||||
| Papalia (2021) [61] | Prospective | Hip | 48 | 61.2 | HA-SC | 1 | 6 | Rapid and significant decrease of VAS pain and LI that was sustained at 6 months |
6MWT 6-Minute Walk Test, ASES American Shoulder and Elbow Surgeons, FIHOA Functional Index for Hand OA, HA hyaluronic acid, HMW molecular weight, IKDC International Knee Documentation Committee, KOOS Knee Injury and Osteoarthritis Outcome Score, LI Lequesne's Algofunctional Index, PRP platelet-rich plasma, RCT randomized controlled trial, VAS visual analog scale, WOMAC Western Ontario and McMaster Universities Arthritis Index