Clinical trial NCT06210542: Precise Treatment of Ceftazidime-Avibactam in Patients With CRO Infections Under the Guidance of TDM and PPK Model
Official title: Precise Treatment of Ceftazidime-Avibactam in Patients With CRO Infections Under the Guidance of TDM and PPK Model
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: ECMO
Carbapenem-Resistant Enterobacteriaceae Infection
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2024-01-18
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: critically ill patients in ICU with CRO infections (including dialysis patients and ECMO patients).

Brief summary: The goal of this study is to evaluate the efficacy and safety of ceftazidime-avibactam(CAZ-AVI) in the treatment of critically ill patients with carbapenem-resistant organisms(CRO) infections (including dialysis patients and extracorporeal membrane oxygenation(ECMO) patients).

Detailed description: This is a prospective observational multicentre study. The study is to obtain the real world data of the efficacy and safety of ceftazidime-avibactam(CAZ-AVI) in the treatment of critically ill patients with carbapenem-resistant organisms(CRO) infections (including dialysis patients and extracorporeal membrane oxygenation(ECMO) patients) by using therapeutic drug monitoring(TDM). A population-pharmacokinetic(PPK) model of CAZ-AV in these patients will be established in this study. The main question it aims to answer is the clinical success rate and microbiological success rate of CAZ-AVI based regimen in the treatment of critically ill patients with CRO infections. According to the clinical practice (symptoms, signs, imaging, culture and drug sensitivity, etc.), the doctor determines the combined regimen of CAZ-AVI, and the combined drugs are used routinely according to their instructions or clinical diagnosis and treatment.

Eligibility criteria: Inclusion Criteria:

1. 18-85 years old.
2. Hospitalized participants in ICU who did not receive Ceftazidime Avibactam treatment within 15 days before joining the study.
3. Participants with severe infection (refer to the 2022 sepsis3.0 guidelines for the definition of severe infection).
4. at least one carbapenem-resistant Gram-negative pathogen (including but not limited to carbapenem-resistant Enterobacteriaceae and / or Pseudomonas aeruginosa) was confirmed by bacterial culture in the primary infection site samples.
5. sufficient respiratory secretions, blood and peritoneal effusion can be obtained within 48 hours before the first administration for bacterial culture and drug sensitivity test.
6. intravenous injection of Ceftazidime Avibactam for more than 72 hours.
7. understand compliance with research procedures and methods, voluntarily participate in this study, and sign informed consent in writing.

Exclusion Criteria:

1. Participants are less than 18.
2. Death within 72 hours after the start of treatment.
3. Known resistance to β-lactam antibacterial drugs including cephalosporins, cephalosporin compound preparations containing β-lactamase inhibitors, or Those with a history of allergies to ceftazidime avibactam sodium for injection and its excipients.
4. No indication for treatment with ceftazidime avibactam.
5. Pregnant and lactating women.

Primary outcomes:
measure: Clinical success rate at the end of treatment and/or the time transfer out of ICU
timeFrame: the end of treatment or the time transfer out of ICU,up to 1 year.
measure: Microbiologic success rate at the end of treatment and/or the time transfer out of ICU
timeFrame: the end of treatment or the time transfer out of ICU,up to 1 year.
Secondary outcomes:
measure: All-cause mortality on day 28 after drug initiation
timeFrame: 28 days from drug initiation
measure: Infection-related mortality during hospitalization in ICU
timeFrame: the end of treatment or the time transfer out of ICU,up to 1 year.
measure: All-cause mortality on 90 days after drug initiation
timeFrame: 90 days from drug initiation
measure: Recurrence rate of infection on day 28 after starting medication
timeFrame: 28 days from drug initiation
measure: Length of ICU Stay
timeFrame: the end of treatment or the time transfer out of ICU,up to 1 year.
measure: Length of Hospital Stay (LOS)
timeFrame: the end of treatment or the time transfer out of ICU,up to 1 year.
measure: Time from ceftazidime-avibactam treatment initiation to symptom improvement
timeFrame: the end of treatment or the time transfer out of ICU,up to 1 year.
Other outcomes:
Locations:
Study officials:
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