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

Phase 2

Terminated

• Conditions: Neoplasms; Febrile Neutropenia
• Interventions: Drug: CAZ-AVI; Drug: Vancomycin; Drug: Linezolid; Drug: Cefepime; Drug: Meropenem; Drug: Piperacillin/tazobactam

• Registration Number: NCT02732327
• Lead Sponsor: Forest Laboratories

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-03-18
• Study First Submitted QC: 2016-04-04
• Study First Posted: 2016-04-08
• Study Start: 2016-05-17
• Primary Completion: 2016-06-27
• Study Completion: 2016-06-27
• Status Verified: 2017-06
• Results First Submitted: 2017-06-22
• Results First Submitted QC: 2017-06-22
• Last Update Submitted: 2017-06-22
• Results First Posted: 2017-07-21
• Last Update Posted: 2017-07-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of Care+Vancomycin or Linezolid	Meropenem	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.
Standard of Care+Vancomycin or Linezolid	Piperacillin/tazobactam	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.
CAZ-AVI + Vancomycin or Linezolid	CAZ-AVI	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.
CAZ-AVI + Vancomycin or Linezolid	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.
CAZ-AVI + Vancomycin or Linezolid	Vancomycin	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.
Standard of Care+Vancomycin or Linezolid	Vancomycin	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.
Standard of Care+Vancomycin or Linezolid	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.
Standard of Care+Vancomycin or Linezolid	Cefepime	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.

Primary Outcome Measures

Name	Time	Method
Percentage of Patients With Favorable Clinical Response at End of Inpatient Intravenous Therapy (EOIV)	Up to Day 14	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.

Trial Locations

Locations (1)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States