Open randomized phase II trial of an extracorporeal endotoxin adsorber in suspected Gram-negative sepsis.

OBJECTIVE: An initial phase II trial to investigate the safety and therapeutic effect of the endotoxin adsorber system EN 500 in septic patients suffering from presumed Gram-negative infection.

DESIGN: Open, controlled, prospective, randomized, multiple-center, parallel-group clinical trial.

SETTING: Intensive care units of 31 university-affiliated and community hospitals in Europe.

PATIENTS: One hundred forty-five patients with a clinical diagnosis of severe sepsis or septic shock due to suspected Gram-negative infection.

INTERVENTIONS: Patients were randomized to receive either standard therapy alone for sepsis (n = 76) or standard therapy plus extracorporeal endotoxin adsorption (n = 67) daily for the first 4 days following study entry.

MEASUREMENTS AND MAIN RESULTS: The primary end point was the proportion of responders (defined as a decrease in Acute Physiology and Chronic Health Evaluation II score by > or =4 points from study entry to day 4). Secondary outcomes were the Sequential Organ Failure Assessment score and its components, length of intensive care unit stay, survival rate, and safety of the adsorber treatment. Patient characteristics at entry were well balanced between the two treatment groups, except for a higher Sequential Organ Failure Assessment score in the adsorber group. On all-subjects-treated analysis, 65% of the adsorber group were responders vs. 57% for the standard (p =.389). A planned interim analysis restricted further enrollment to patients with peritonitis, in whom a slightly higher proportion of responders was observed with the adsorber treatment (69%) vs. standard treatment (54%, p =.159). There were no differences in survival, but adsorption treatment in peritonitis patients was associated with trends toward a reduction in length of intensive care unit stay and a more rapid decline in plasma endotoxin concentrations. There was a significantly greater reduction in platelet count with the adsorber; however, this did not require extra treatment.

CONCLUSIONS: The endotoxin adsorber system did not result in a significantly improved primary end point in patients with presumed Gram-negative sepsis. In patients with peritonitis, the adsorber treatment likewise did not result in significantly improved Acute Physiology and Chronic Health Evaluation II scores. There were no clinically important side effects. These results provide encouragement for further study of adsorber treatment in patients with high likelihood of Gram-negative sepsis (e.g., peritonitis).