Source: Medicines & Healthcare Products Regulatory Agency (GB) Publisher: Baxter Healthcare Ltd Caxton Way Thetford Norfolk IP24 3SE United Kingdom
Pharmacotherapeutic group: local hemostatics, ATC code: B02BC; tissue adhesives
ATC code: V03AK
ARTISS can replace sutures or staples when used for fixation of skin grafts to burned or otherwise injured wound areas. ARTISS can be used as an adjunct to sutures or staples to adhere and seal skin flaps in cases where sutures/staples are expected to yield unsatisfactory results with respect to postoperative hematoma or seroma formation.
The fibrin adhesion system initiates the last phase of physiological blood coagulation. Conversion of fibrinogen into fibrin occurs by the splitting of fibrinogen into fibrin monomers and fibrinopeptides. The fibrin monomers aggregate and form a fibrin clot. Factor XIIIa, which is activated from factor XIII by thrombin, crosslinks fibrin. Calcium ions are required for the conversion of fibrinogen and the crosslinkage of fibrin.
As wound healing progresses, increased fibrinolytic activity is induced by plasmin, and decomposition of fibrin to fibrin degradation products is initiated. Proteolytic degradation of fibrin is inhibited by anti-fibrinolytics. Aprotinin is present in ARTISS (frozen) as an antifibrinolytic to prevent premature degradation of the clot.
For efficacy, in vivo studies in an animal model closely imitating the situation in patients were used. ARTISS (frozen and lyophilized presentations) demonstrated efficacy regarding sealing autologous split skin grafts and mesh grafts.
ARTISS (frozen) was investigated for fixation of split thickness sheet skin grafts in burn patients in a prospective, randomised, controlled, multicenter clinical study. In each of the 138 patients, two comparable test sites were identified. In one test site the skin graft was fixed with ARTISS in the other test site the graft was fixed with staples (control). ARTISS proved to be non-inferior to staples with respect to the primary efficacy endpoint, complete wound closure at Day 28 was evaluated by a blinded evaluator panel from photographs. This was achieved in 55/127 patients (43.3%) treated with ARTISS (frozen) and 47/127 patients (37%) treated with staples.
With respect to secondary endpoints, ARTISS showed a significantly lower incidence and size of hematoma/seroma on Day 1 (p < 0.0001 for incidence as well as size). Incidence and area of engraftment on Day 5 and wound closure on Day 14, as well as area of wound closure on Day 28 were not different. ARTISS was also superior to staples with respect to patient satisfaction (p < 0.0001) and patients experienced significantly less anxiety about pain with ARTISS than with staples (p < 0.0001). Moreover, ARTISS was significantly superior to staples with respect to the investigator’s assessment of quality of graft adherence, preference of fixation method and satisfaction with graft fixation, overall quality of healing and overall rate of healing (p < 0.0001).
Thirty-seven (37) pediatric patients aged 1.1 to 18 years were evaluated in this trial.
Eighteen (18) of these patients were 6 years old or younger.
Dosage used in clinical trials was the same for pediatric and adult patients.
ARTISS is intended for epilesional use only. Intravascular administration is contraindicated. As a consequence, intravascular pharmacokinetic studies were not performed in man.
Pharmacokinetic studies in different species of laboratory animals were not conducted.
Fibrin sealants/hemostatics are metabolized in the same way as endogenous fibrin by fibrinolysis and phagocytosis.
No preclinical safety data are available for ARTISS (thrombin 4 IU/ml). Toxicity studies were done with Fibrin Sealants containing thrombin 500 IU/ml, as representative for products containing thrombin 4 IU/ml. Single-dose toxicity studies in rats and rabbits indicated no acute toxicity of Fibrin Sealant VH S/D (500 IU/ml). Fibrin Sealant VH S/D (500 IU/ml) also proved well tolerated in wound healing models in rats and rabbits, and in in vitro human fibroblast cultures.
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