Trial Outcomes & Findings for Retrospective Analysis of Real World Use of Ceftazidime-avibactam in the Management of Gram Negative Infections (NCT NCT04628572)

Results Overview

The clinical symptom improvement was assessed as per the clinical judgement of the physician and reported as symptom improved and symptom worsened.

Recruitment status

COMPLETED

Target enrollment

189 participants

Primary outcome timeframe

Day 3 after ceftazidime-avibactam initiation

Results posted on

2024-08-14

Participant Flow

Participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included in this retrospective study. Data was collected from electronic health records or participant's medical records. Data was collected for the period from 01-Jun-2019 to 01-Apr-2020 (approximately 10 months).

Participant milestones

Participant milestones
Measure	Ceftazidime-Avibactam Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Overall Study STARTED	189
Overall Study COMPLETED	189
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Age, Continuous	55.6 Years STANDARD_DEVIATION 17.8 • n=189 Participants
Sex: Female, Male Female	66 Participants n=189 Participants
Sex: Female, Male Male	123 Participants n=189 Participants

PRIMARY outcome

Timeframe: Day 3 after ceftazidime-avibactam initiation

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

The clinical symptom improvement was assessed as per the clinical judgement of the physician and reported as symptom improved and symptom worsened.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=103 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Clinical Symptom Improvement at Day 3 Symptom Improved	82 Participants
Number of Participants With Clinical Symptom Improvement at Day 3 Symptom Worsened	21 Participants

PRIMARY outcome

Timeframe: Day 7 after ceftazidime-avibactam initiation

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

The treatment success was defined as resolution of all signs and symptoms of the infection based on the clinician's judgment and the treatment protocol/algorithm followed at the respective centers. The treatment success in terms of clinical outcome was classified as clinical success (resolution of all signs and symptoms of the infection), clinical failure (persistence of signs and symptoms from baseline) and indeterminate (there is not enough information to conclude whether the antibiotic regimen containing ceftazidime-avibactam was a clinical failure or a success).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=83 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Treatment Success at Day 7 Clinical Success	66 Participants
Number of Participants With Treatment Success at Day 7 Clinical Failure	12 Participants
Number of Participants With Treatment Success at Day 7 Clinical Indeterminate	5 Participants

PRIMARY outcome

Timeframe: Day 14 or End of Treatment after ceftazidime-avibactam initiation, whichever was earlier

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

The treatment success was defined as resolution of all signs and symptoms of the infection based on the clinician's judgment and the treatment protocol/algorithm followed at the respective centers. The treatment success in terms of clinical outcome was classified as clinical success (resolution of all signs and symptoms of the infection), clinical failure (persistence of signs and symptoms from baseline) and indeterminate (there is not enough information to conclude whether the antibiotic regimen containing ceftazidime-avibactam was a clinical failure or a success).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=59 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Treatment Success at Day 14 or End of Treatment Clinical Success	45 Participants
Number of Participants With Treatment Success at Day 14 or End of Treatment Clinical Failure	13 Participants
Number of Participants With Treatment Success at Day 14 or End of Treatment Clinical Indeterminate	1 Participants

PRIMARY outcome

Timeframe: Day 7 after ceftazidime-avibactam initiation

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Microbiological success was defined as absence of causative pathogen from appropriately obtained specimens at the site of infection (eradication) and repeat cultures were not performed/clinically indicated in a participant who had a clinical response of cure (presumed eradication).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=38 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Microbiological Success at Day 7 Eradication	31 Participants
Number of Participants With Microbiological Success at Day 7 Presumed Eradication	7 Participants

PRIMARY outcome

Timeframe: Day 14 or End of Treatment after ceftazidime-avibactam initiation, whichever was earlier

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Microbiological success was defined as absence of causative pathogen from appropriately obtained specimens at the site of infection (eradication) and repeat cultures were not performed/clinically indicated in a participant who had a clinical response of cure (presumed eradication).

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=41 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Microbiological Success at Day 14 or End of Treatment Eradication	24 Participants
Number of Participants With Microbiological Success at Day 14 or End of Treatment Presumed Eradication	17 Participants

PRIMARY outcome

Timeframe: Up to 30 days post treatment completion with ceftazidime-avibactam, death or discharge; whichever was first (Up to maximum of 49 days)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence at any dose that: resulted in death, was life threatening (immediate risk of death), required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions), resulted in congenital anomaly/birth defect. All AEs that did not meet the criteria for "serious" were considered as non-serious. Adverse events with explicit attribution to any Pfizer drug that appeared in the reviewed information (defined per the participant population and study period specified in the protocol) were reported. Explicit attribution was not inferred by temporal relationship between drug administration and an AE, but was based on a causality assessed by a healthcare provider linking drug administration and AE.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Serious Adverse Events and Non-Serious Adverse Events With Explicit Attribution to Ceftazidime-Avibactam Serious adverse events	0 Participants
Number of Participants With Serious Adverse Events and Non-Serious Adverse Events With Explicit Attribution to Ceftazidime-Avibactam Non-serious adverse events	0 Participants

SECONDARY outcome

Timeframe: Baseline (before initiation of initial antibiotic therapy)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Source of infection included hospital-acquired infection, healthcare-associated infection, and community-acquired infection.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants Classified According to Source of Infection at Baseline for Which Ceftazidime-Avibactam Was Used Hospital-Acquired Infection	72 Participants
Number of Participants Classified According to Source of Infection at Baseline for Which Ceftazidime-Avibactam Was Used Healthcare Associated Infection	65 Participants
Number of Participants Classified According to Source of Infection at Baseline for Which Ceftazidime-Avibactam Was Used Community-Acquired Infection	52 Participants

SECONDARY outcome

Timeframe: Baseline (before the initiation of initial antibiotic therapy)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

The indications for use of ceftazidime-avibactam at baseline including urinary tract infection, intra-abdominal infection and nosocomial pneumonia and any other indication were reported.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants According to Indication at Baseline for Which Ceftazidime-Avibactam Was Used Nosocomial Infection	55 Participants
Number of Participants According to Indication at Baseline for Which Ceftazidime-Avibactam Was Used Urinary Tract Infection	55 Participants
Number of Participants According to Indication at Baseline for Which Ceftazidime-Avibactam Was Used Intra-abdominal Infection	30 Participants
Number of Participants According to Indication at Baseline for Which Ceftazidime-Avibactam Was Used Others	49 Participants

SECONDARY outcome

Timeframe: Up to Day 14 or End of treatment after ceftazidime-avibactam initiation, whichever was earlier

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

In this outcome measure dose (median of daily dose) of ceftazidime-avibactam was reported till Day 14 or End of treatment whichever was earlier.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Dose of Ceftazidime - Avibactam	2500 Milligrams Interval 1000.0 to 2500.0

SECONDARY outcome

Timeframe: Up to Day 14 or End of treatment after ceftazidime-avibactam initiation, whichever was earlier

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Number of participants according to frequency of administration (twice daily \[BID\], once daily \[OD\] and thrice daily \[TID\]) of ceftazidime-avibactam is reported in this outcome measure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants According to Frequency of Administration BID	71 Participants
Number of Participants According to Frequency of Administration OD	22 Participants
Number of Participants According to Frequency of Administration TID	96 Participants

SECONDARY outcome

Timeframe: Up to Day 14 or End of treatment after ceftazidime-avibactam initiation, whichever was earlier

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Duration of Administration of Ceftazidime - Avibactam	2.1 Hours Standard Deviation 0.8

SECONDARY outcome

Timeframe: Up to Day 14 or End of treatment after ceftazidime-avibactam initiation, whichever was earlier

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Total Duration of Therapy of Ceftazidime-Avibactam	6.92 Days Standard Deviation 4.1

SECONDARY outcome

Timeframe: Up to Day 14 or End of treatment after ceftazidime-avibactam initiation, whichever was earlier

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants Who Received Concomitant Antibiotics With Ceftazidime-Avibactam	156 Participants

SECONDARY outcome

Timeframe: 90 days prior to current hospital admission

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With History of Antibiotic Exposure	126 Participants

SECONDARY outcome

Timeframe: Baseline (before the initiation of initial antibiotic therapy)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

In this outcome measure, the gram-negative organisms identified at baseline was reported. One participant could have more than one gram-negative bacteria identified.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=84 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants According to Identified Gram Negative Organisms Klebsiella pneumoniae	57 Participants
Number of Participants According to Identified Gram Negative Organisms Escherichia Coli	15 Participants
Number of Participants According to Identified Gram Negative Organisms Pseudomonas aeruginosa	11 Participants
Number of Participants According to Identified Gram Negative Organisms Klebsiella species	4 Participants
Number of Participants According to Identified Gram Negative Organisms Enterobacter species	1 Participants
Number of Participants According to Identified Gram Negative Organisms Enterobacter cloacae	1 Participants
Number of Participants According to Identified Gram Negative Organisms Proteus mirabilis	1 Participants
Number of Participants According to Identified Gram Negative Organisms Pseudomonas species	1 Participants
Number of Participants According to Identified Gram Negative Organisms Other	1 Participants

SECONDARY outcome

Timeframe: Baseline (before the initiation of initial antibiotic therapy)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=47 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Identified Pathogens Susceptible to Ceftazidime-Avibactam	34 Participants

SECONDARY outcome

Timeframe: Up to 30 days post treatment completion, death or discharge; whichever was first (Up to maximum of 49 days)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Duration of hospital stay was calculated based on 1) total number of consecutive days the participant was treated in the hospital from admission to discharge during their initial hospitalization; 2) the total number of days of hospitalization between diagnosis of infection and discharge; 3) the total number of days the participant was treated in the hospital after ceftazidime-avibactam initiation up to hospital discharge, including the first day of treatment.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Duration of Hospital Stay	23.1 Days Standard Deviation 15.1

SECONDARY outcome

Timeframe: Up to 30 days post treatment completion, death or discharge; whichever was first (Up to maximum of 49 days)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

Intensive care unit length of stay was calculated based on 1) the total number of consecutive or non-consecutive days the participant was treated in the ICU during their initial hospitalization; and 2) the total number of days the participant was treated in the ICU after ceftazidime-avibactam initiation, including the first day of treatment.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=162 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Duration of Stay in Intensive Care Unit (ICU)	15.7 Days Standard Deviation 14.3

SECONDARY outcome

Timeframe: Up to 30 days post treatment completion with ceftazidime-avibactam death or discharge; whichever was first (Up to maximum of 49 days)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours. Here, 'Overall Number of Participants Analyzed' signifies participants evaluable for this outcome measure.

In this outcome measure number of participants were reported as per their healthcare resource utilization data, abstracted from the participant medical records. Healthcare resources included: mechanical ventilation, computed tomography (CT)/magnetic resonance imaging (MRI), tracheostomy, hemodialysis, surgical intervention, percutaneous procedures and other procedures.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=109 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants According to Healthcare Resource Utilization Mechanical ventilation	82 Participants
Number of Participants According to Healthcare Resource Utilization CT/MRI imaging	59 Participants
Number of Participants According to Healthcare Resource Utilization Tracheostomy	36 Participants
Number of Participants According to Healthcare Resource Utilization Hemodialysis	25 Participants
Number of Participants According to Healthcare Resource Utilization Surgical intervention	16 Participants
Number of Participants According to Healthcare Resource Utilization Percutaneous procedures	5 Participants
Number of Participants According to Healthcare Resource Utilization Other procedure (Other healthcare resources utilized)	22 Participants

SECONDARY outcome

Timeframe: Up to 30 days post treatment completion with ceftazidime-avibactam, death or discharge; whichever was first (Up to maximum of 49 days)

Population: Analysis population included all participants who received ceftazidime-avibactam for at least 48 hours.

Number of participants with recurrence of infection during hospital stay, including re-infection and relapse up to 30 days post treatment completion with ceftazidime-avibactam, death or discharge; whichever occurred first was summarized in this outcome measure.

Outcome measures

Outcome measures
Measure	Ceftazidime-Avibactam n=189 Participants Eligible participants who were hospitalized with Gram negative infections and received ceftazidime-avibactam for at least 48 hours in routine clinical practice were included.
Number of Participants With Recurrence of Infection	8 Participants

Adverse Events

Ceftazidime-Avibactam

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Pfizer Clinical Trials.gov Call Center

Pfizer Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Publication restrictions are in place

Restriction type: OTHER