An evaluation of the hemodynamic effects of HA-1A human monoclonal antibody.

Abstract

We sought to determine whether there might be acute changes in hemodynamics attributable to HA-1A, a monoclonal antibody to endotoxin, in patients with presumed Gram-negative sepsis. Post hoc analysis of a multicenter, randomized, double-blind, placebo-controlled study. A total of 543 patients with severe sepsis presumed to be caused by Gram-negative bacteria who were enrolled in a clinical trial to evaluate the efficacy and safety of HA-1A human monoclonal antibody. Patients were randomly assigned to receive either 100 mg of HA-1A or placebo. Patients were grouped by the study drug, HA-1A, or placebo, and the presence or absence of Gram-negative bacteremia. Hemodynamic variables were monitored from before, until 72 hrs after infusion of the study drug. For the entire study population (n = 543), no changes over time attributable to study drug were noted in the mean arterial pressure (p > .19), heart rate (p > .53) or the need for vasopressor administration (p > .62). One hundred ninety-seven patients underwent pulmonary artery catheterization and had hemodynamic data available from before the infusion of HA-1A or placebo until at least 12 hrs after infusion. Evaluating all 197 patients on an intent to treat basis demonstrated no significant differences over time in cardiac index (p > .15), oxygen delivery index (p > .43), or left ventricular stroke work index (p > .48) between patients who received HA-1A and those patients receiving placebo. Grouping patients by the presence of Gram-negative bacteremia and study drug received also failed to demonstrate any significant difference attributable to HA-1A in mean arterial pressure (p > .54), heart rate (p > .84), cardiac index (p > .13), oxygen delivery index (p > .05), or left ventricular stroke work index (p > .48) between populations. There is no apparent relationship between the administration of HA-1A, the presence of Gram-negative bacteremia, and hemodynamic profiles over the 72-hr study period.