Drotrecogin alfa (recombinant human activated protein C) in severe sepsis--a New Zealand viewpoint

Sepsis is a serious and increasing worldwide intensive care problem. In response to intensivists' concerns over the benefits, risks and financial implications of the use of drotrecogin alfa (recombinant human activated protein C), the first adjunctive therapy for sepsis licensed in New Zealand, the New Zealand Region of the Australian and New Zealand Intensive Care Society (ANZICS) requested an advisory statement from a working party of New Zealand intensivists. We reviewed (a) the PROWESS study of drotrecogin alfa recombinant; (b) the submission made by the sponsoring company to the FDA; (c) recent discussions and an economic evaluation of the use of the agent; (d) Australian pharmaceutical benefits scheme positive recommendations; (e) guidelines produced by the Eli Lilly Australian Advisory Board; (f) Australian hospital decisions on availability; and (g) New Zealand pricing and payment arrangements. We then formulated suggested New Zealand guidelines. We recommend that hospital pharmacy and therapeutics committees review the agent now. If the agent is made available for use, we recommend that: (a) specialists prescribing the agent be required to contribute clinical data to a national register of patients, (b) patients considered for treatment should first be treated with all appropriate surgical and medical therapy for severe sepsis with high illness severity in an intensive care unit by an intensivist; (c) patients considered for treatment should not have severe comorbidity or predetermined treatment limitations or contraindications to the agent in the original phase III study; and (d) patients should be considered only if seen to be not clearly improving after a six-hour period of intensive treatment. Once a decision has been made to treat with drotrecogin alfa, treatment should commence as soon as possible and within 24 hours of meeting criteria. Although the agent is recommended for use in adults, it may be reasonable to treat some older children. Despite high cost and moderate benefit, it may be reasonable to treat highly selected New Zealand patients with drotrecogin alfa.