Comparative Study of Ceftazidime-Avibactam Versus Standard of Care as Therapy in Febrile Neutropenic Adults With Cancer

A Single-Center, Randomized, Open-label, Prospective, Comparative Study to Determine the Efficacy, Safety, and Tolerability of Ceftazidime-Avibactam (CAZ-AVI) Plus Vancomycin or Linezolid Versus Standard of Care Plus Vancomycin or Linezolid as Empiric Therapy in Febrile Neutropenic Adults With Cancer

This study will evaluate the effect, safety, and tolerability of ceftazidime-avibactam (CAZ-AVI) plus vancomycin or linezolid compared to standard of care plus vancomycin or linezolid as empiric therapy in febrile neutropenic adults with cancer

Study Overview

• Status: Terminated
• Conditions: Neoplasms; Febrile Neutropenia
• Intervention / Treatment: Drug: CAZ-AVI; Drug: Vancomycin; Drug: Linezolid; Drug: Cefepime; Drug: Meropenem; Drug: Piperacillin/tazobactam

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with neutropenic fever who have existing malignancy or have undergone hematopoietic stem cell transplantation
• Requires hospitalization for intravenous (IV) empiric antibiotic therapy

Exclusion Criteria:

• Fungal or viral infection requiring additional therapy
• Known acute viral hepatitis
• Known to be human immunodeficiency virus (HIV) positive
• Expected requirement for hemodialysis while on study therapy
• Received >24 hours of systemic antibacterial therapy within 72 hours of initiation of inpatient IV study drug
• Past or current history of epilepsy or seizure disorder
• Evidence of immediately life-threatening disease, progressively fatal disease, or life expectancy of 3 months or less.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAZ-AVI + Vancomycin or Linezolid; Ceftazidime-Avibactam (CAZ-AVI) 2.5 mg intravenous (IV) infusion every 8 hours for 5 to 14 days, duration determined by the investigator, plus vancomycin 15 mg/kg IV or linezolid 600 mg IV every 12 hours. A switch to open-label oral or IV therapy (IV therapy for outpatient or home administration per local standard of care [SOC]) may be allowed after at least 72 hours (ie, minimum of 9 doses for CAZ-AVI) of inpatient IV study drug.	Drug: CAZ-AVI; Ceftazidime-Avibactam (2 g ceftazidime and 0.5 g avibactam); Drug: Vancomycin; 15 mg/kg; Other Names: Vancocin; Drug: Linezolid; 600 mg; Other Names: Zyvox
Active Comparator: Standard of Care+Vancomycin or Linezolid; Standard of Care (cefepime 2 g IV infusion every 8 hours or meropenem 1 g IV infusion every 8 hours or piperacillin/tazobactam 4.5 g IV infusion every 6 hours for 5 to 14 days, duration determined by the investigator) plus vancomycin 15 mg/kg IV or linezolid 600 mg IV every 12 hours. A switch to open-label oral or IV therapy (IV therapy for outpatient or home administration per local SOC) may be allowed after at least 72 hours (ie, minimum of 9 doses for SOC therapies, except piperacillin/tazobactam, which is a minimum of 12 doses) of inpatient IV study drug.	Drug: Vancomycin; 15 mg/kg; Other Names: Vancocin; Drug: Linezolid; 600 mg; Other Names: Zyvox; Drug: Cefepime; 2 g; Other Names: Maxipime; Drug: Meropenem; 1 g; Other Names: Merrem; Drug: Piperacillin/tazobactam; 4.5 g; Other Names: Zosyn

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV)	Favorable clinical response is defined as resolution of all acute signs and symptoms of the primary infection or improvement to such an extent that no additional antibacterial therapy is required as assessed by the investigator. Due to study termination and limited enrollment, outcome measures were not analyzed.	Up to Day 14

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Study Director: David Melnick, M.D., Allergan

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2016
• Primary Completion (Actual): June 27, 2016
• Study Completion (Actual): June 27, 2016

Study Registration Dates

• First Submitted: March 18, 2016
• First Submitted That Met QC Criteria: April 4, 2016
• First Posted (Estimate): April 8, 2016

Study Record Updates

• Last Update Posted (Actual): July 21, 2017
• Last Update Submitted That Met QC Criteria: June 22, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Body Temperature Changes; Heat Stress Disorders; Neutropenia; Hyperthermia; Fever; Febrile Neutropenia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; beta-Lactamase Inhibitors; Vancomycin; Linezolid; Meropenem; Piperacillin; Tazobactam; Piperacillin, Tazobactam Drug Combination; Cefepime
• Other Study ID Numbers: CAZ-MD-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No