The Study of Drotrecogin Alfa (Activated) in a Subpopulation of Adult Patients With Severe Sepsis

Lilly

Status and phase: Completed; Phase 4

Conditions: Sepsis

Treatments: Drug: Drotrecogin alfa (activated)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00045760

F1K-MC-EVCM

7252, 6669

F1K-MC-EVCL

Details and patient eligibility

About

Severe sepsis is defined as a systemic inflammatory response syndrome that results from infection and is associated with acute organ dysfunction. It usually results from bacterial infections, but it may occur in response to other pathogens, such as fungi, viruses, and parasites.

Full description

Drotrecogin alfa (activated), a recombinant form of human activated protein C, is the first therapeutic intervention shown to reduce all-cause mortality in severe sepsis. In the Phase 3 study (F1K-MC-EVAD; PROWESS), 1690 patients were randomly assigned to receive a 96-hour intravenous infusion of drotrecogin alfa (activated) 24 micrograms/kg/h or placebo (850 patients and 840 patients, respectively). Overall, administration of drotrecogin alfa (activated) yielded a clinically significant reduction in 28-day all-cause mortality: 24.7% of drotrecogin alfa (activated) patients died versus 30.8% of placebo patients (19.4% relative risk reduction; p=0.005; Bernard et al. 2001). The only safety concern noted in the Phase 3 trial was an increased risk of serious bleeding among drotrecogin alfa (activated) patients (3.5% versus 2.0% of placebo patients). The difference between the two treatment groups in the number of patients who experienced a serious bleeding event was due to the greater number of drotrecogin alfa (activated) patients who experienced a serious bleeding event that was related to a procedure (for example, bleeding that resulted from the placement of a catheter or nephrostomy tube). The number of patients who experienced spontaneous serious bleeding events was similar between the two treatment groups.

The Regulatory authorities have approved the use of drotrecogin alfa (activated) in severe sepsis patients with a high level of disease severity and risk of death. Thus, the regulatory authorities have requested a study evaluating drotrecogin alfa (activated) in a specific subpopulation of patients with severe sepsis and at lower risk of death.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients with severe sepsis.
• Presence of a suspected or proven infection.
• One or more sepsis-associated organ failure.

Exclusion criteria

• Are indicated for the treatment with drotrecogin alfa (activated) in the investigative site country.
• Are contraindicated for treatment with drotrecogin alfa (activated) under the applicable label in the investigative site country.
• Platelet count <30,000/mm3.
• Are receiving therapeutic heparin.