Second Course of Recombinant Human Activated Protein C Delivered to a Severely Septic Patient After Recent Surgery

Readministration of drotrecogin alfa (activated) in an adult with severe sepsis

“…Currently there is minimal evidence regarding the readministration of drotrecogin alfa in patients with repeated episodes of sepsis, [9][10][11] but the limited information available suggests that the risk of antibody formation is minimal in patients who receive single or multiple courses of drotrecogin alfa. 9 A recent study evaluated the development of anti-APC antibodies among patients in four clinical studies of drotrecogin alfa.…”

“…7 A recent study showed that the risk of the development of antibodies after administration of the agent is low 9 ; however, there are limited data to indicate whether clinical outcomes are worse in patients receiving multiple courses of drotrecogin alfa. [7][8][9][10][11] Here we report the case of a patient with severe sepsis who was successfully treated with two courses of the agent.…”

Evaluation of anti‐activated protein C antibody development in patients with severe sepsis from four clinical studies with drotrecogin alfa (activated)

“…There is limited clinical experience with the safety of administration of DAA to patients with severe sepsis who have been previously exposed to DAA, including a few published case reports [26][27][28][29][30]. Additional experience was obtained in the ADDRESS trial, in which nine patients with a history of prior exposure to DAA were randomized to receive DAA; there was no evidence of a hypersensitivity reaction among these nine patients, and no evidence of anti-APC antibody formation among the six patients tested as part of this report.…”

“…The institutional review board at each investigative site approved the study protocol, and all patients or their authorized representatives gave written informed consent. The prespecified sampling times were baseline, day 14 (days 12-21), and day 28 (days [22][23][24][25][26][27][28], with an additional sample being collected at day 60 (days 42-60) in the three postapproval DAA studies (EVBF, ADDRESS, and XPRESS). For samples collected outside of these predefined windows, additional time windows were used for data analyses, and these were day 7 (days 1-11), day 40 (days 29-41) and post-day 60.…”

The safety profile of drotrecogin alfa (activated)

“…sick individuals, even after repeated administration. DrotAA re-administration is not contraindicated [ 8 ]; a few anecdotal reports describe repeated re-administration in a clinical setting [ 26 ].…”