How do I screen patients for severe sepsis?

Resources and Reimbursement

To assist you in assessing the role of Xigris in treatment of high-risk severe sepsis, the following resources are available:

eLearning Module: With this self-paced, interactive presentation, you can learn about the clinical manifestation of severe sepsis and the benefits of treatment with Xigris
Video Library: Hear from healthcare professionals about diagnosing severe sepsis and assessing risk of death using the APACHE II scoring system
Slide Kits, Learning Modules, and Animations: Our slide kit discusses the impact of severe sepsis on institutional outcomes, and our three learning modules contain information about identifying severe sepsis and the efficacy and safety of Xigris in its treatment. Animations include the Sepsis Continuum animation, Mortality Risk Assessment animation, and Organ Dysfunction Assessment animation
Benefit/Risk Analyzer: This animation will help you determine if Xigris is right for your patient by comparing the benefits of Xigris therapy with the potential risks

If you would like information about reimbursement for Xigris, click here to learn more about the Xigris Reimbursement Hotline and the Xigris Treatment Support Program (XTSP).

IMPORTANT SAFETY INFORMATION

Xigris is indicated for the reduction of mortality in adult patients with severe sepsis (sepsis associated with acute organ dysfunction) who have a high risk of death (eg, as determined by APACHE II*).

Xigris is not indicated in adult patients with severe sepsis and lower risk of death. Xigris is not indicated in pediatric patients with severe sepsis.

CONTRAINDICATIONS

Xigris increases the risk of bleeding. Xigris is contraindicated in patients with the following clinical situations in which bleeding could be associated with a high risk of death or significant morbidity:

Active internal bleeding
Recent (within 3 months) hemorrhagic stroke
Recent (within 2 months) intracranial or intraspinal surgery, or severe head trauma
Trauma with an increased risk of life-threatening bleeding
Presence of an epidural catheter
Intracranial neoplasm or mass lesion or evidence of cerebral herniation

Xigris is contraindicated in patients with known hypersensitivity to drotrecogin alfa (activated) or any component of this product.

WARNINGS

Bleeding

Bleeding is the most common serious adverse effect associated with Xigris therapy. Each patient being considered for therapy with Xigris should be carefully evaluated and anticipated benefits weighed against potential risks associated with therapy.

Certain conditions, many of which led to exclusion from the Phase 3 trial, are likely to increase the risk of bleeding with Xigris therapy. Therefore, for patients with severe sepsis who have one or more of the following conditions, the increased risk of bleeding should be carefully considered when deciding whether to use Xigris therapy:

Concurrent therapeutic heparin to treat an active thrombotic or embolic event
Platelet count <30,000 x 10⁶/L, even if the platelet count is increased after transfusions
Prothrombin time-INR >3.0
Recent (within 6 weeks) gastrointestinal bleeding
Recent administration (within 3 days) of thrombolytic therapy
Recent administration (within 7 days) of oral anticoagulants or glycoprotein IIb/IIIa inhibitors
Recent administration (within 7 days) of aspirin >650 mg per day or other platelet inhibitors
Recent (within 3 months) ischemic stroke
Intracranial arteriovenous malformation or aneurysm
Known bleeding diathesis
Chronic severe hepatic disease
Any other condition in which bleeding constitutes a significant hazard or would be particularly difficult to manage because of its location

Invasive procedures increase the risk of bleeding among patients receiving Xigris. Xigris should be discontinued prior to the performance of invasive surgical procedures or other procedures associated with special risks for bleeding.

Mortality in patients with single organ dysfunction and recent surgery

Among the small number of patients enrolled in PROWESS with single organ dysfunction and recent surgery (surgery within 30 days prior to study treatment) all-cause mortality was numerically higher in the Xigris group (28-day: 10/49; in-hospital: 14/48) compared to the placebo group (28-day: 8/49; in-hospital: 8/47).

In an analysis of the subset of patients with single organ dysfunction and recent surgery from a separate, randomized, placebo-controlled study (ADDRESS) of septic patients not at high risk of death all-cause mortality was also higher in the Xigris group (28-day: 67/323; in-hospital: 76/325) compared to the placebo group (28-day: 44/313; in-hospital: 62/314). Patients with single organ dysfunction and recent surgery may not be at high risk of death irrespective of APACHE II score and therefore not among the indicated population.

Clinicians should consider continuing prophylactic heparin when initiating Xigris therapy, unless discontinuation is considered medically necessary

In a randomized study of prophylactic heparin versus placebo in 1935 adult severe sepsis patients treated with Xigris, mortality and the rate of serious adverse events were increased in the subgroup of 434 patients whose low-dose heparin was stopped on study entry by randomization to placebo. This finding was based on prospectively defined exploratory subgroup analyses; however, the explanation for the finding is unclear.

ADVERSE REACTIONS

Bleeding is the most common adverse reaction associated with Xigris therapy. In the Phase 3 study, serious bleeding events were observed during the 28-day study period in 3.5% of Xigris-treated and 2.0% of placebo-treated patients. The difference in serious bleeding occurred primarily during infusion. The incidence of intracranial hemorrhage (ICH) was 0.2% for Xigris-treated and 0.1% for placebo-treated patients. ICH has been reported in Xigris-treated patients in non-placebo controlled trials with an incidence of approximately 1% during infusion. The risk of ICH may be increased in patients with risk factors for bleeding such as severe coagulopathy and severe thrombocytopenia. Should clinically important bleeding occur, immediately stop the Xigris infusion.

*APACHE (Acute Physiology And Chronic Health Evaluation).

Please refer to the full Prescribing Information for Xigris.