**7. Clinical results and applications**

The DAC® hydrogel received the CE mark at the end of year 2013. The available kit (www. coatingdac.com or www.dac-coating.com) is composed of a prefilled syringe, containing 300 mg sterile DAC® powder, that is filled at surgery with a solution of 5 mL sterile water for injection, eventually mixed with the desired antibiotic(s); this allows to obtain, in approximately 3–5 min, the antibiotic-loaded hydrogel, at a DAC® concentration of 6% (w/v) and at an antibiotic concentration usually ranging from 20 mg/mL to 50 mg/mL, depending on the surgeon's choice. The surgeons can choose the antibiotic from among a list of antibacterials previously tested as being compatible with the hydrogel (Novagenit SRL, data on file). A few minutes after reconstitution, the hydrogel can be directly spread onto the implant, which is then inserted into the body in the usual way. If necessary, once reconstituted, the hydrogel may remain at ambient temperature for up to 4 h.

Two large multicenter, randomized, prospective clinical trials were undertaken in Europe, within the 7th European Framework Programme (project # 277988), funded by the European Commission.

In a first trial, a total of 380 patients, scheduled to undergo primary (n = 270) or revision (n = 110) total hip (N = 298) or knee (N = 82) joint replacement with cementless or hybrid (partially cemented) implants were included [59, 60]. The patients were randomly assigned, in six European orthopedic centers, to receive an implant either with the DAC® coating, intraoperatively loaded with antibiotics (treatment group), or without the coating (control group). Pre- and postoperative assessment of clinical scores, wound healing, laboratory tests and X-ray exams were performed at fixed time intervals. Overall, 373 patients were available at a mean follow-up of 14.5 ± 5.5 months (range 6–24). On average, a volume of 8.3 mL hydrogel was used to coat an implant. The most often used antibiotics were vancomycin and gentamicin at a concentration of 5% and 3.2%, respectively. Fifteen patients received an implant with a combined vancomycin and meropenem antibiotic coating; four patients received an implant coated with teicoplanin 5% or ceftazidime 5% or amphotericin B 5%, all in a second-stage procedure for previous infection. Eleven surgical site infections were observed in the control group and only one in the treatment group (6% vs. 0.6%; P = 0.003). No local or systemic side effects related to the DAC® hydrogel coating were reported and no detectable interference with implant osteointegration was noted.

In the other multicenter, prospective study, 256 patients, undergoing osteosynthesis for a closed fracture, were randomly assigned, in 5 European orthopedic centers, to receive the antibiotic-loaded DAC® coating or to a control group, without coating. At a mean follow-up of


**Table 1.** Summary of the main results of the published clinical multicenter trials on DAC® hydrogel coating in orthopedics and trauma.

18.1 ± 4.5 months (range 12–30), 253 patients were available for evaluation. On average, 5.7 mL (range: 1–10 mL) of DAC® hydrogel was needed to coat the implant. Gentamicin and vancomycin were the most used antibiotics, at concentration of, respectively, 4% or 2%. Six surgical site infections (4.6%) were observed in the control group compared to none in the treated group (P < 0.02). No local or systemic side effects related to DAC® hydrogel coating were observed and no detectable interference with bone healing was reported [61, 62] (cf. **Table 1**).

Preliminary results of the possible use of the DAC® hydrogel coating in one-stage exchange of infected prosthesis did also recently show the efficacy and safety of the device in this challenging application [63]. Further studies are currently under way concerning joint replacement in bone tumors, spine surgery, exposed fractures and dentistry.
