Efficacy and Safety of CAZ-AVI in the Treatment of Infections Due to Carbapenem-resistant G- Pathogens in Chinese Adults

Study Overview
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Brief Summary
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This is an open-label, randomized, multi-center, interventional, active-controlled Phase 4 study to evaluate the efficacy and safety of CAZ-AVI versus BAT in the treatment of infected participants with selected infection types (Hospital Acquired Pneumonia [HAP] (including Ventilator-Associated Pneumonia [VAP]); Complicated Urinary-Tract Infection [cUTI]; Complicated Intra-Abdominal Infection [cIAI]; Bloodstream Infection [BSI]) due to carbapenem-resistant Gram-negative pathogens in China.This study will be an estimation study. The statistical inference will be based on point estimate and confidence interval.

Official Title
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AN OPEN-LABEL, RANDOMIZED, MULTI-CENTER, ACTIVE-CONTROLLED STUDY TO ESTIMATE THE EFFICACY AND SAFETY OF CEFTAZIDIME-AVIBACTAM (CAZ-AVI) VERSUS BEST AVAILABLE TREATMENT (BAT) IN THE TREATMENT OF INFECTIONS DUE TO CARBAPENEM-RESISTANT GRAM-NEGATIVE PATHOGENS IN CHINESE ADULTS

Conditions
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Bacteremia, Urinary Tract Infection, Acute Pyelonephritis, Hospital Acquired Pneumonia, Ventilator-associated Pneumonia, Intra-abdominal Infection

Intervention / Treatment
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* Drug: Zavicefta, Ceftazidime-Avibactam
* Drug: Best Available Treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female >18 years of age Participant must have a diagnosis of an infection (HAP/VAP, cUTI, cIAI, BSI) due to confirmed carbapenem-resistant aerobic Gram-negative pathogens, requiring administration of IV antibacterial therapy Participant who had received appropriate prior empiric antibacterial therapy for a carbapenem-resistant pathogen must meet at least 1 of the following criteria: no or no more than 24h; worsening of objective symptoms or signs after at least 48 hours of antibacterial therapy; no change of objective symptoms or signs after at least 72 hours of antibacterial therapy. Capable of giving signed informed consent Exclusion Criteria: Other medical or psychiatric condition may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Participant is expected to require more than 21 days of treatment Participants who need more than 3 systemic antibiotics as part of best available treatment (BAT) Previous administration with an investigational drug within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Participant is pregnant or breastfeeding. Acute Physiology and Chronic Health Evaluation (APACHE) II score >30 or <10 using the most recent available data.

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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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAZ-AVI<br>ceftazidime 2g plus avibactam 0.5g | Drug: Zavicefta, Ceftazidime-Avibactam<br>* CAZ-AVI 2.5 g (2 g ceftazidime + 0.5 g avibactam) administered IV as a 2 hour infusion every 8 hours. Dose adjustments are available for participants with CrCL ≤50 mL/min.<br>|
| Active Comparator: Best Available Treatment<br>Based on investigative site practice and local epidemiology and guideline | Drug: Best Available Treatment<br>* main treatment expected to be used as either monotherapy or in combination are colistin, tigecycline, fosfomycin, amikacin, and meropenem<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of participants in Microbiologically Modified Intent to Treat (mMITT) analysis set having clinical cure |  | Test of Cure (TOC, Day 21 - 25) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The percentage of participants in mMITT analysis set having clinical cure |  | End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose) | 
| The percentage of participants in Microbiologically Evaluable (ME) analysis set having clinical cure |  | End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose) | 
| The percentage of participants in ME analysis set having clinical cure |  | Test of Cure (TOC, Day 21-Day 25) | 
| The percentage of participants in mMITT analysis set having favorable microbiological response |  | Test of Cure(TOC, Day 21-Day 25) | 
| The percentage of participants in mMITT analysis set having favorable microbiological response |  | End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose) | 
| The percentage of participants in ME analysis set having favorable microbiological response |  | End of Treatment (EOT, participants were followed after the last IV dose but no later than 24 hours after the last IV dose) | 
| The percentage of participants in ME analysis set having favorable microbiological response |  | Test of Cure(TOC, Day 21-Day 25) | 
| The percentage of participants who have died due to any cause |  | Day 28 | 
| The number of treatment-emergent adverse events |  | up to 32 days after the last dose of study intervention | 
| The percentage of participants experiencing the AEs |  | up to 32 days after the last dose of study intervention |