Efficacy and Safety of Resatorvid in Patients With Sepsis-induced Cardiovascular and Respiratory Failure
Condition: Sepsis
MeSH terms: Sepsis; Toxemia; Respiratory Insufficiency
Intervention: Resatorvid; Placebo
Intervention description: Resatorvid 1.2 mg/kg emulsion, injection for 30 minutes and resatorvid 2.4 mg/kg per-day emulsion, injection, continuous infusion for 96 hours.; Resatorvid placebo-matching emulsion, injection for 30 minutes and resatorvid placebo-matching emulsion, injection, continuous infusion for 96 hours.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Systemic Inflammatory Response Syndrome; Septic Shock; Septicemia; Drug Therapy

Summary:

      The purpose of this study is to determine the effect of resatorvid on subjects with sepsis.
    

Eligibility criteria:

        Inclusion Criteria

          -  Suspected or proven bacterial or fungal infection for which patient is receiving
             parenteral antimicrobial therapy.

          -  Developed at least 3 of the 4 following systemic inflammatory response syndrome
             criteria within 36 hours prior to start of study drug administration:

               -  A temperature from any site greater than 38°C (greater than 100.4°F) or a core
                  temperature less than 36°C (less than 96.8°F).

               -  Heart rate of greater than 90 beats per minute. If subject has a known medical
                  condition (eg, heart block) or is receiving treatment (eg, beta blocker) that
                  would prevent tachycardia, only 2 of the remaining 3 criteria for systemic
                  inflammatory response syndrome must be met.

               -  Respiratory rate of greater than 20 breaths per min or arterial partial pressure
                  of carbon dioxide of less than 32 mm Hg or mechanical ventilation for an acute
                  process.

               -  A total white blood cell absolute count greater than 12,000 cells per mm3 or less
                  than 4,000 cells/mm3; or a white blood cell differential count showing greater
                  than 10% immature (band) forms.

          -  Has septic shock diagnosed within 36 hours prior to study drug administration..

          -  Has developed respiratory failure within 36 hours prior to study drug administration.

          -  Females of childbearing potential who are sexually active must agree to use adequate
             contraception, and can neither be pregnant nor lactating from Screening throughout the
             duration of the study.

        Exclusion Criteria

          -  Received any investigational compound within 30 days (or 5 half-lives of the drug,
             whichever is longer) prior to the initiation of the study drug infusion or is
             participating in another investigational study, not including investigational
             compound, without prior approval from the Vanderbilt Coordinating Center or the
             sponsor.

          -  Currently receiving any immunosuppressive therapy (excluding glucocorticoids) such as
             methotrexate, azathioprine, anti tumor necrosis factor alpha, or a cancer related
             chemotherapeutic agent.

          -  Known history of glucose-6-phosphate dehydrogenase deficiency.

          -  Methemoglobin level of greater than or equal to 5% at pretreatment period or has a
             known history of methemoglobinemia.

          -  Moribund and death is considered imminent.

          -  Prior to the onset of sepsis, the subject would not otherwise have been expected to
             survive 28 days or to complete a functional recovery due to a pre-existing unstable
             medical condition (eg, a recent acute cerebral hemorrhage or infarct, a recent acute
             unstable myocardial infarction, severe traumatic injury).

          -  Poorly controlled or metastatic neoplasm.

          -  The participant, the participant's family or physician is not committed to full
             aggressive management or the presence of an unstable medical condition makes the
             receipt of full aggressive management support unlikely in the view of the coordinating
             center.

          -  Severe end stage chronic respiratory failure or lung disease that significantly
             impairs physical functioning equivalent to that of New York Heart Association
             functional classification III or IV.

          -  Documented history of moderate to severe chronic heart failure as defined by New York
             Heart Association functional classification III or IV.

          -  Received electrocardioversion for a pulse-less rhythm or chest compressions during
             their current hospitalization.

          -  Known to be immunocompromised such as subjects with human immunodeficiency virus and a
             CD4 count less than 50 mm3, primary immune deficiency or chronic lymphocytic leukemia.

          -  Chronic end stage hepatic failure or significant sequelae of chronic hepatic failure
             (eg, esophageal varices, jaundice, chronic ascites) or Child-Pugh hepatic impairment
             Classification C.

          -  In a chronic vegetative state or has a similar long-term neurological impairment,
             where continued aggressive care would be unlikely.

          -  Acute third degree burns involving more than 30% of body surface area within 120 hours
             of first qualifying organ failure.

          -  Known hypersensitivity to sulphonamides.

          -  Known hypersensitivity to components of resatorvid; for example, is allergic to eggs,
             egg products, or soybeans.