Regulatory Decision Summary for Vistaseal

Vistaseal is a kit consisting of two prefilled syringes of fibrinogen and thrombin solutions assembled in a syringe holder. An airless applicator for mixing the two solutions and for application by dripping or spraying is also provided. Vistaseal is applied during surgery only by a surgeon who has received prior training. A thin layer of Vistaseal is applied to entirely cover the bleeding tissue.

Marketing authorization was supported by three (3) clinical studies in 500 patients treated with Vistaseal and 377 patients treated with a control treatment (manual compression with hemostatic pads or oxidized regenerated cellulose). Among these patients, 23 pediatric patients aged less than 18 years old were evaluated only for safety during the training phase of the studies. Efficacy and safety was established during the second phase of the studies, in a total of 613 adult patients and one adolescent involved in 26% vascular graft surgeries (Study IG1101), 37% liver tissue surgeries (Study IG1102), and 37% urologic and gynecologic soft tissue surgeries (Study IG1103).

In all three studies, the efficacy measurement was the cessation of bleeding (hemostasis) at 4 minutes after treatment application. Vistaseal was shown to provide a fast and effective fibrin sealant, in order to achieve hemostasis during various surgical procedures. A greater proportion of patients achieve hemostasis with Vistaseal compared to manual compression, while similar proportions of patients achieve hemostasis with Vistaseal or oxidized regenerated cellulose. Overall, the incidence of persistent bleeding was lower with Vistaseal compared to the control treatments (manual compression or oxidized regenerated cellulose).

There are inherent safety risks associated with the use of Vistaseal that are known for this class of fibrin sealant products. These include the potential risks of infectious agents (e.g. viruses) due to the human sourced components, risk of blood clots if the product is inadvertently injected in blood vessels, and air or gas embolism if applied by spraying using pressurized gas. However, risk of infectious agents has been reduced according to standard guidelines including blood donor screening and manufacturing processes. In addition, the risk for air or gas embolism is negligible with Vistaseal since pressurized gas is not required for spraying with the airless applicator.

During vascular graft procedures (Study IG1101), two serious adverse drug reactions were reported in the Vistaseal treatment group, including vascular graft complication (1.2% of patients) and skin infection (0.6%). During liver surgeries (Study IG1102), blood clots were reported in two patients (1.2%) in the Vistaseal treatment group, although expected with the medical condition of these patients. During soft tissue surgeries (Study IG1103), one patient (0.6%) reported abdominal wound reopening and infection of the abdominal lining in the Vistaseal treatment group.

Overall, the benefit in the use of Vistaseal is considered favorable over the risks, with risk mitigations described in the Product Monograph.