Real-World Observational Study Of Zavicefta to Characterize Use Patterns

Study Overview
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Brief Summary
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This is a non-interventional medical chart review study aiming to examine the treatment patterns, effectiveness, and safety of ceftazidime-avibactam in approximately 12 countries (including but not limited to Austria, France, Germany, Greece, Italy, Spain, United Kingdom, Russia, Argentina, Colombia, Brazil, and Mexico), with possible expansion to other countries as ceftazidime-avibactam is launched. Eligible patients are adults who have been treated with ceftazidime-avibactam in routine practice at participating sites since 01 January, 2018 onwards or since the date of launch in the country if it is posterior to 01 January, 2018. As this is an observational study, patients will be treated based on the standard of care at the discretion of their physician. No drugs will be supplied for this study and patients will receive treatment through standard local practice.

Detailed Description
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This observational study will include approximately 700 hospitalized patients with a gram-negative infection, who have received at least one dose of ceftazidime-avibactam. Patients will be recruited in approximately 62 sites across 12 countries in Europe (including Russia) and Latin America. Patients will be followed from ceftazidime-avibactam initiation until 60 days post hospital discharge, mortality, withdrawal from the study, or loss-to-follow-up, whichever occurs first. Data will be abstracted from medical records using an electronic case report form (eCRF). Baseline data include patient socio-demographics, medical history, and clinical and microbiological characteristics of the infection treated. Follow-up data will include details of treatment over time and clinical, microbiological, and healthcare resource utilization outcomes. Evaluation of clinical success will be performed in patients with at least ≥72 hours of exposure to ceftazidime-avibactam. Safety will be evaluated in all patients exposed to at least one dose of the product.

Official Title
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Real-World Observational Study of Zavicefta (Registered) (Ceftazidime-avibactam) to Characterize Use Patterns, Effectiveness and Safety - EZTEAM Study

Conditions
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Infection

Intervention / Treatment
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* Other: Zavicefta Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hospitalized patient ≥18 years old or considered an adult in accordance with the age of majority in the participant's country of residence at the time of treatment with ceftazidime-avibactam. Patient received ≥1 dose of ceftazidime-avibactam in routine practice at participating site since 01 January, 2018 onwards or since the date of launch in the country if it is after 01 January, 2018. Patient underwent microbiologic sampling ≤5 days before the initiation of ceftazidime-avibactam (irrespective of results and actual bacteriological identification). Patient has all required essential data elements which include: Start and stop dates of ceftazidime-avibactam, Start and stop dates of prior antibiotic therapy used for the index infection, Type of combined antibiotic therapy (if applicable) and start and stop dates of any antibiotic combined with ceftazidime-avibactam. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study where required by local regulations. Exclusion Criteria: Patients must not meet any of the following exclusion criteria to be eligible: The patient is enrolled in any clinical trial of an investigational product. Patients who are enrolled in non-interventional studies (NISs) (e.g. registries) are eligible for inclusion. The patient has received ceftazidime-avibactam in a compassionate care program setting. The patient was exposed to ceftazidime-avibactam before use for the index infection.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Zavicefta Treatment|Non-interventional - Retrospective Chart Review|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Gram-Negative Pathogens According to the Multi-Drug Resistance After Treatment Initiation: FAS72+ Population | Multi-drug resistance was defined as the isolate being non-susceptible to at least one agent in more than or equal to (>=) 3 antimicrobial categories, excluding the therapeutic classes to which the pathogen was intrinsically resistant. The number of gram-negative pathogens classified according to the antibiotic resistance to specified antibiotics after treatment initiation were reported in this outcome measure. | After treatment initiation up to 60 days post hospital discharge, in-hospital death, withdrawal from the study, or lost to follow-up, whichever occurred first maximum of 464 days (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Readmitted to the Hospital During the 30 Days After Initial Discharge: FAS72+ Population | The number of participants readmitted to the hospital during the 30 days after initial discharge were reported in this outcome measure. | Up to 30 days after initial discharge (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Readmitted to the Hospital During the 60 Days After Initial Discharge: FAS72+ Population | The number of participants readmitted to the hospital during the 60 days after initial discharge were reported in this outcome measure. | Up to 60 days after initial discharge (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Reason for Readmission to the Hospital: FAS72+ Population | The number of participants classified according to the reason for readmission to the hospital were reported in this outcome measure. One participant could have more than 1 reason for readmission to the hospital. | At readmission to the hospital, up to maximum of 60 days post initial hospital discharge (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to the Healthcare Resource Utilized During the Hospitalization: FAS72+ Population | The number of participants classified according to the healthcare resource utilization during the hospitalization were reported in this outcome measure. One participant could have utilized more than 1 healthcare resource during hospitalization. | During index hospitalization maximum of 418 days (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to All Wards Attended During Hospitalization: FAS72+ Population | The number of participants classified according to all wards attended during hospitalization were reported in this outcome measure. | During index hospitalization maximum of 418 days (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Reason for Initiating Antibiotics: FAS 72+ Population | The number of participants classified according to reason for initiating specific antibiotics combined with ceftazidime-avibactam were reported in this outcome measure. One participant could have received more than 1 antibiotics and there could be more than 1 reason for initiating antibiotics. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Reason for Discontinuing Antibiotics: FAS 72+ Population | The number of participants classified according to reason for discontinuing specific antibiotics combined with ceftazidime-avibactam were reported in this outcome measure. One participant could have received more than 1 antibiotics and there could be more than 1 reason for discontinuing antibiotics. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Whose Samples Were Taken for Clinical Microbiological Evaluation After End of Ceftazidime-Avibactam Therapy: Microbiology Outcomes Dataset (MOD) Population | The number of participants whose samples were taken for clinical microbiological evaluation after end of ceftazidime-avibactam therapy were reported in this outcome measure. | From end of index therapy up to 60 days after hospital discharge, in-hospital death, withdrawal from study, or lost to follow-up, whichever occurred first maximum of 464 days (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Type of Specimen Taken for Clinical Microbiological Evaluation After End of Ceftazidime-Avibactam Therapy: MOD Population | The number of participants classified according to the type of specimen taken for clinical microbiological evaluation after end of ceftazidime-avibactam therapy were reported in this outcome measure. More than 1 type of specimen could have been taken from 1 participant. | From end of index therapy up to 60 days after hospital discharge, in-hospital death, withdrawal from study, or lost to follow-up, whichever occurred first maximum of 464 days (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to the Pathogens Identified From the Microbiological Culture After Treatment Initiation: MOD Population | The number of participants classified according to the pathogens identified from the microbiological culture after treatment initiation were reported in this outcome measure. | After treatment initiation up to 60 days post hospital discharge, in-hospital death, withdrawal from the study, or lost to follow-up, whichever occurred first maximum of 464 days (from the data evaluated in approximately 40 months of the study) | 
| Number of Gram-Negative Pathogens According to the Susceptibility to Antibiotics After Treatment Initiation: FAS72+ Population | The number of gram-negative pathogens according to the susceptibility to specific antibiotics after treatment initiation were reported in this outcome measure. | After treatment initiation up to 60 days post hospital discharge, in-hospital death, withdrawal from the study, or lost to follow-up, whichever occurred first maximum of 464 days (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Who Received at Least One Dose of Ceftazidime-Avibactam Classified According to Type of Usage as Monotherapy or Combination Therapy: FAS 72+ Population | Number of participants who received at least one dose of ceftazidime-avibactam according to type of use as monotherapy or combination therapy was reported in this outcome measure. Index date was start date of ceftazidime-avibactam. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Who Received at Least One Dose of Ceftazidime-Avibactam Classified According to Type of Usage as Monotherapy or Combination Therapy: FAS72- Population | Number of participants who received at least one dose of ceftazidime-avibactam according to type of use as monotherapy or combination therapy was reported in this outcome measure. | From start of index treatment to end of index treatment (maximum 3 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Total and Daily Dose of Ceftazidime-Avibactam: FAS72+ Population | The total cumulative dose and daily dose of ceftazidime-avibactam was reported in this outcome measure. Total cumulative dose was defined as the sum of all doses received. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Total and Daily Dose of Ceftazidime-Avibactam: FAS72- Population | The total cumulative dose and daily dose of ceftazidime-avibactam was reported in this outcome measure. Total cumulative dose was defined as the sum of all doses received. | From start of index treatment to end of index treatment (maximum 3 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Frequency of Dosing: FAS72+ Population | Number of participants classified according to frequency of dose (once daily [OD], every other day [QOD], post-dialysis, each 48 hours [h], three times daily [TID], twice daily [BD], four times daily [QID], once loading dose [an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose], every three days, once, etc.,) for ceftazidime-avibactam were reported in this outcome measure. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Frequency of Dosing: FAS72- Population | Number of participants classified according to frequency of dose (once daily [OD], every other day [QOD], each 48 hours [h], continuous infusion per 48 hours [c/48 h], three times daily [TID], twice daily [BD], four times daily [QID], one dose, loading dose [an initial higher dose of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose] etc.,) for ceftazidime-avibactam were reported in this outcome measure. | From start of index treatment to end of index treatment (maximum 3 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Total Duration of Administration of Ceftazidime-Avibactam: FAS72+ Population | Total duration of administration was calculated as stop date of administration of ceftazidime-avibactam minus start date of ceftazidime-avibactam administration plus 1. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Total Duration of Administration of Ceftazidime-Avibactam: FAS72- Population | Total duration of administration was calculated as stop date of administration of ceftazidime-avibactam minus start date of ceftazidime-avibactam administration plus 1. | From start of index treatment to end of index treatment (maximum 3 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Reason for Discontinuation of Ceftazidime-Avibactam: FAS72+ Population | Number of participants according to the reasons for discontinuation of ceftazidime-avibactam were reported in this outcome measure. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Reason for Discontinuation of Ceftazidime-Avibactam: FAS72- Population | Number of participants according to the reasons for discontinuation of ceftazidime-avibactam were reported in this outcome measure. | From start of index treatment to end of index treatment (maximum 3 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Antibiotics Used Concurrently: FAS 72+ Population | The number of participants classified according to antibiotics used concurrently with ceftazidime-avibactam were reported in this outcome measure. Participants could have received more than 1 antibiotic. | From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Type of Clinical Evaluation Outcome at Initial Hospitalization: Clinical Outcomes Dataset (COD) Population | The number of participants classified according to type of clinical evaluation outcome as success, failure or indeterminate. Success: resolution of all signs and symptoms of infection with no need for escalation of antimicrobials for gram-negative coverage. Failure: inadequate response to ceftazidime-avibactam therapy or resistant, worsening, or new recurrent signs and symptoms at the end of ceftazidime-avibactam therapy. Indeterminate: there was not enough information to conclude whether the antibiotic regimen containing ceftazidime-avibactam was a clinical failure or a success. | At initial hospitalization (from the data evaluated in approximately 40 months of this study) | 
| Number of Participants Classified According to Type of Clinical Evaluation Outcome 60 Days Post-Discharge: Clinical Outcomes Dataset (COD) Population | The number of participants classified according to type of clinical evaluation outcome as success, failure or indeterminate. Success: resolution of all signs and symptoms of infection with no need for escalation of antimicrobials for gram-negative coverage. Failure: inadequate response to ceftazidime-avibactam therapy or resistant, worsening, or new recurrent signs and symptoms at the end of ceftazidime-avibactam therapy. Indeterminate: there was not enough information to conclude whether the antibiotic regimen containing ceftazidime-avibactam was a clinical failure or a success. | 60 days after hospital discharge (from the data evaluated in approximately 40 months of this study) | 
| Number of Participants Classified According to Type of Clinical Evaluation Outcome 60 Days Post-Treatment: Clinical Outcomes Dataset (COD) Population | The number of participants classified according to type of clinical evaluation outcome as success, failure or indeterminate. Success: resolution of all signs and symptoms of infection with no need for escalation of antimicrobials for gram-negative coverage. Failure: inadequate response to ceftazidime-avibactam therapy or resistant, worsening, or new recurrent signs and symptoms at the end of ceftazidime-avibactam therapy. Indeterminate: there was not enough information to conclude whether the antibiotic regimen containing ceftazidime-avibactam was a clinical failure or a success. | 60 days post treatment (from the data evaluated in approximately 40 months of this study) | 
| Number of Participants With Microbiological Treatment Outcome as Success: MOD Population | The number of participants with microbiological treatment outcome as success were reported in this outcome measure. Success was defined as: absence of causative pathogen from appropriately obtained specimens at the site of infection. | Up to 14 days post first dose of ceftazidime-avibactam (from the data evaluated in approximately 40 months of the study) | 
| Number of Participants Classified According to Antibiotics Used for Current Infection Before Ceftazidime-Avibactam: FAS72+ Population | The number of participants classified according to antibiotics used (Yes or No) for current infection before ceftazidime-avibactam were reported in this outcome measure. | Up to 90 days prior to index date (from the data evaluated in approximately 40 months of this study) | 
| Number of Participants Classified According to Reason for Discontinuation for Prior Antibiotic Therapy: FAS72+ Population | The number of participants classified according to reason for discontinuing for prior antibiotic therapy were reported in this outcome measure. One participant could have more than 1 reason of discontinuation for prior antibiotic therapy. | Up to 90 days prior to index date (from the data evaluated in approximately 40 months of this study) | 
| Percentage of Participants Who Died During Index Hospitalization | In hospital-mortality was defined as deaths occurring after treatment initiation but before hospital discharge. The percentage of participants who died during index hospitalization were reported in this outcome measure. | During index hospitalization, maximum of 418 days (from the data evaluated in approximately 40 months of this study) | 
| Percentage of Participants Who Died Within the 30 Days After Hospital Discharge (Including In-Hospital Mortality): FAS72+ Population | 30-day mortality was defined as deaths occurred from index treatment up to within 30 days after hospital discharge including in-hospital mortality. | From index treatment up to 30 days post hospital discharge, maximum of 434 days (from the data evaluated in approximately 40 months of this study) | 
| Percentage of Participants Who Died Within 60 Days After Hospital Discharge (Including In-Hospital Mortality): FAS72+ Population | 60-day mortality was defined as deaths occurred from index treatment up to within 60 days after hospital discharge including in-hospital mortality. | From index treatment up to 60 days post hospital discharge, maximum of 434 days (from the data evaluated in approximately 40 months of this study) | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. AE included both SAEs and non-SAEs. SAE was defined as any untoward medical occurrence at any dose that: resulted in death, was life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was important medical event; required hospitalization or prolongation of existing hospitalization. Only AEs and SAEs with explicit attribution to ceftazidime-avibactam that appeared in the reviewed information and scenarios involving drug exposure to ceftazidime-avibactam, which included exposure during pregnancy, exposure during breastfeeding, medication error, overdose, misuse, extravasation, lack of efficacy and occupational exposure associated with the use of ceftazidime-avibactam were collected in the study. | From index date up to 60 days after hospital discharge, in-hospital death, withdrawal from the study, or lost to follow-up, whichever occurred first maximum of 464 days (from the data evaluated in approximately 40 months of the study) | 
| Duration of Hospital Stay: FAS72+ Population | Hospital length of stay (LOS) was defined as date of hospital discharge minus date of hospital admission plus 1. The duration of hospital stay of participants were reported in this outcome measure. | From index date up to hospital discharge, in-hospital death, withdrawal from the study, or lost to follow-up, whichever occurred first maximum of 418 days (from the data evaluated in approximately 40 months of the study) | 
| Total Duration of ICU Stay: FAS72+ Population | Duration of ICU stay was defined as date of ICU discharge minus date of ICU admission plus 1. The total duration of ICU stay of participants were reported in this outcome measure. | During index hospitalization, maximum up to 418 days (from the data evaluated in approximately 40 months of the study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ceftazidime-avibactam, Zavicefta