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

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02732327
• Collaborator: (none)
• Enrollment: 2
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.3
• Patients Per Site Per Month: 1.5

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Neoplasms; Febrile Neutropenia	Drug: CAZ-AVI; Drug: Vancomycin; Drug: Linezolid; Drug: Cefepime; Drug: Meropenem; Drug: Piperacillin/tazobactam	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 2 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 17, 2016
• Actual Primary Completion Date: Jun 27, 2016
• Actual Study Completion Date: Jun 27, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: David Melnick, M.D., Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Forest Laboratories
• ClinicalTrials.gov Identifier: NCT02732327
• Other Study ID Numbers: CAZ-MD-13
• First Posted: Apr 8, 2016
• Last Update Posted: Jul 21, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Neutropenia; Febrile Neutropenia; Hyperthermia; Fever; Vancomycin; Meropenem; Tazobactam; Linezolid; Piperacillin; Cefepime; Piperacillin, Tazobactam Drug Combination

Study Results

Participant Flow

Recruitment Details	The planned sample size was 100 patients; however, the sponsor discontinued the study due to the fact that the study no longer aligned with the revised clinical development plan and commercial strategy for CAZ-AVI. A total of 2 patients were enrolled and completed the study.

Arm/Group Title	CAZ-AVI + Vancomycin or Linezolid	Standard of Care+Vancomycin or Linezolid
Arm/Group Description	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 (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.
Period Title: Overall Study
STARTED	0	2
COMPLETED	0	1
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	CAZ-AVI + Vancomycin or Linezolid	Standard of Care+Vancomycin or Linezolid	Total
Arm/Group Description	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 (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.	Total of all reporting groups
Overall Participants	0	2	2
Age, Customized (Number) [Number]
Between 18 and 65 years	2 Infinity	0 0%
Sex: Female, Male (Count of Participants)
Female	0 NaN	0 0%
Male	2 Infinity	2 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CAZ-AVI + Vancomycin or Linezolid	Standard of Care+Vancomycin or Linezolid
Arm/Group Description	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 (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.
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Due to termination of the study, adverse events were not coded.
Arm/Group Title	CAZ-AVI + Vancomycin or Linezolid		Standard of Care+Vancomycin or Linezolid
Arm/Group Description	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 (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.
All Cause Mortality
	CAZ-AVI + Vancomycin or Linezolid		Standard of Care+Vancomycin or Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	CAZ-AVI + Vancomycin or Linezolid		Standard of Care+Vancomycin or Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	CAZ-AVI + Vancomycin or Linezolid		Standard of Care+Vancomycin or Linezolid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		2/2 (100%)
Gastrointestinal disorders
Abdominal Pain	0/0 (NaN)		1/2 (50%)
Respiratory, thoracic and mediastinal disorders
Cough	0/0 (NaN)		1/2 (50%)
Vascular disorders
Thrombosis	0/0 (NaN)		1/2 (50%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.