Comparative Study To Determine The Efficacy, Safety, And Tolerability Of Ceftolozane-Tazobactam
Condition: Other Infectious Diseases
MeSH terms: Communicable Diseases; Infections
Intervention: Cefepime; Ceftolozane; Laboratory Biomarker Analysis; Meropenem; Piperacillin-Tazobactam; Tazobactam
Intervention description: Given IV; Given IV; Correlative studies; Given IV; Given IV; Given IV
Intervention MeSH terms: Meropenem; Tazobactam; Piperacillin; Cefepime; Piperacillin, Tazobactam Drug Combination; Ceftolozane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 100.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Other infectious diseases; Febrile neutropenic adults with cancer; Ceftolozane-Tazobactam; Cefepime; Meropenem; Piperacillin/Tazobactam

Summary:

      The goal of this clinical research study is to learn if the study drug ceftolozane-tazobactam
      is more effective in controlling febrile neutropenia (fever and low white blood cell counts)
      than using approved antibiotics in patients with cancer. The safety of ceftolozane-tazobactam
      will also be studied.

      This is an investigational study. Ceftolozane-tazobactam is FDA approved and commercially
      available to treat certain types of infections. It is not approved for the treatment of
      febrile neutropenia, either by itself or in combination with other antibiotics. Its use to
      treat febrile neutropenia is investigational.

      All other antibiotics given on this study are FDA approved and commercially available for the
      treatment of infections. However, only cefepime is specifically FDA approved to treat febrile
      neutropenia. The study doctor can explain how the study drugs are designed to work.

      Up to 100 participants will take part in this study. All will be enrolled at MD Anderson.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has provided written informed consent, and has the willingness and ability to comply
             with all study procedures

          -  Patients with neutropenic fever who have existing malignancy or have undergone
             hematopoietic stem cell transplantation; neutropenic fever is defined as the presence
             of neutropenia defined by: 1) absolute neutrophil count (ANC) < 500 cells/mm^3 or has
             an ANC that is expected to decrease to < 500 cells/mm^3 within 48 hours of trial entry
             and fever defined as: 2) single oral temperature measurement of > 101 degree
             Fahrenheit (F) (38.3 degree Celsius [C]) or a temperature of > 100.4 degree F (38.0
             degree C) sustained over a 1-hour period

          -  Requires hospitalization for IV empiric antibiotic therapy

          -  If female: not breastfeeding; agrees to not attempt to become pregnant during the
             study; is surgically sterile or at least 2-years postmenopausal, or if of childbearing
             potential, has negative screening serum pregnancy test (if serum pregnancy test
             results are not available at the time of enrollment, a negative urine pregnancy test
             is required within 24 hours.); if of childbearing potential (including being < 2 years
             postmenopausal), is willing to practice sexual abstinence or use an effective dual
             form of contraception with her partner (eg, 2 barrier methods, barrier method plus
             hormonal method) during treatment and for ≥ 28 days after the last dose of any study
             therapy (IV or oral)

        Exclusion Criteria:

          -  History of any hypersensitivity or allergic reaction to any cephalosporin antibiotic
             or tazobactam

          -  Fever suspected to be caused by a noninfectious cause (eg, fever related to drug or
             blood product administration)

          -  Confirmed fungal infection (eg, Pneumocystis jirovecii etiology in patients with
             pneumonia) that justifies adding additional empiric antimicrobial therapy (eg,
             antifungals)

          -  Confirmed viral infection that justifies adding additional empiric antiviral therapy
             (eg, ganciclovir, foscarnet)

          -  Known acute viral hepatitis

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > 5 times the
             upper limit of normal (x ULN); patients with values > 3 x ULN and < 5 x ULN are
             eligible if the value is acute and directly related to the infectious process being
             treated

          -  Total bilirubin > 3 x ULN unless isolated hyperbilirubinemia is directly related to
             the acute infection or due to known Gilbert disease; manifestations of end-stage liver
             disease, such as ascites or hepatic encephalopathy

          -  Known to be human immunodeficiency virus positive

          -  Severely impaired renal function, defined as creatinine clearance (CrCl) =< 30 mL/min
             estimated by the Cockcroft-Gault formula

          -  Expected requirement for hemodialysis while on study therapy

          -  Received > 24 hours of IV antibacterial therapy (with study drugs) within 72 hours of
             the initiation of inpatient IV study drug for treatment of suspected infection;
             antibiotic prophylaxis and oral antibiotics is allowed; prophylactic use of antiviral
             or antifungal medication is permitted

          -  Requirement for any non-study potentially effective concomitant systemic antibacterial
             therapy

          -  Past or current history of epilepsy or seizure disorder; exception: well-documented
             febrile seizure of childhood

          -  Evidence of immediately life-threatening disease, progressively fatal disease, or life
             expectancy of 3 months or less (eg, moribund or with shock unresponsive to fluid
             replacement)

          -  Unable or unwilling to adhere to the study-specified procedures and restrictions

          -  Any condition that would make the patient, in the opinion of the investigator,
             unsuitable for the study (eg, would place a patient at risk or compromise the quality
             of the data

          -  Participation in any other ongoing ceftolozane/tazobactam trial