Clinical trial NCT06811727: CONTinuous Infusion Versus Intermittent Dosing of ceftaZidime/AVIbactam in Critically Ill Patients
Official title: CONTinuous Infusion Versus Intermittent Dosing of ceftaZidime/AVIbactam in Critically Ill Patients With Klebsiella Pneumoniae OXA-48 or Pseudomonas Aeruginosa Infections: A Single-centre Randomized Open-label Trial (ZAVICONT)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Severe Infection
Keywords: ceftazidime/avibactam
continuous infusion
critically ill
ICU
Klebsiella pneumoniae OXA-48
Pseudomonas aeruginosa
Lead sponsor: Clinical Hospital Centre Zagreb
Sponsor class: OTHER
Collaborators: name: UHC Zagreb, Zagreb, Croatia
name: Daniel Lovrić
name: Mirna Momčilović
First posted: 2025-02-06
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Ceftazidime/avibactam (CZA) is an essential treatment option for managing infections caused by multidrug-resistant (MDR) gram-negative (G-) bacteria, including Klebsiella pneumoniae OXA-48 and carbapenem-resistant Pseudomonas aeruginosa. Critically ill intensive care unit (ICU) patients frequently exhibit altered pharmacokinetics (PK) of CZA, potentially compromising optimal PK/pharmacodynamic (PD) target attainment with standard dosing regimens. This study compares the efficacy of continuous infusion (CI) versus conventional intermittent dosing (ID) of CZA in critically ill ICU patients with severe infections caused by K. pneumoniae OXA-48 or P. aeruginosa.

This single-centre, randomized, open-label trial will be conducted at a tertiary care hospital within the University Hospital Centre in Zagreb, Croatia, with a 1:1 allocation ratio. One hundred forty critically ill ICU patients requiring CZA treatment will be randomized to receive either ID (2 g/0.5 g every 8 hours over 2 hours) or an equivalent dose in CI (6 g/1.5 g continuously over 24 hours).

The primary outcome is the microbiological success rate. Secondary outcomes include clinical success rate, time to symptom improvement, length of ICU and hospital stay, 28-day all-cause mortality, pathogen recurrence rate, time to weaning from mechanical ventilation, cumulative vasoactive-inotropic score, adverse events, and the ratio of ceftazidime plasma concentration to the pathogen's minimum inhibitory concentration (C/MIC).

This trial seeks to provide evidence on the optimal administration strategy for CZA in critically ill ICU patients with severe infections due to MDR G- pathogens.


Eligibility criteria: Inclusion Criteria:

1. General

   1. Age above or equal to 18 years of age.
   2. Able to provide informed consent personally or by his/her next of kin, as requested by the Ethics Committee.
2. Disease-specific

   1. Critically ill patients requiring admission to the intensive care unit (medical or surgical).
   2. Diagnosed with severe infections.
   3. At least one microbiological sample positive for Klebsiella pneumoniae OXA-48 or Pseudomonas aeruginosa.
   4. Requiring a prescription for ceftazidime/avibactam, by clinical judgement

Exclusion Criteria:

1. General

   1. Known or suspected hypersensitivity to ceftazidime/avibactam, excipients, or any other cephalosporin antibacterial agent. Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other β-lactam antibacterial agent (e.g. penicillins, monobactams or carbapenems).
   2. Withdrawal of informed consent.
   3. Age above 85 years of age.
   4. Female who is pregnant or breast-feeding.
   5. Participation (i.e. signed informed consent) in any other interventional clinical trial of an approved or non-approved antibacterial agent within 30 days before screening.
   6. Any disorder which, in the investigator's opinion, might jeopardize the participant's safety or compliance with the protocol.
2. Laboratory values

   1. Severe neutropenia before or during ceftazidime/avibactam administration.
3. Medical conditions

   1. Death within 48 hours following randomization.
   2. Concomitant acquired immunodeficiency syndrome.
   3. Presence or history of malignant neoplasms or in situ carcinomas.
   4. Duration of ceftazidime/avibactam administration is shorter than 72 hours.

Primary outcomes:
measure: microbiological success rate
timeFrame: 28 days
Secondary outcomes:
measure: clinical success rate
timeFrame: 28 day
measure: time to symptoms improvement
timeFrame: 28 day
measure: length of ICU stay
timeFrame: 28 day
measure: length of hospital stay
timeFrame: 28 day
measure: all-cause 28-day mortality after ceftazidime/avibactam initiation
timeFrame: 28 day
measure: pathogen recurrence rate on day 28
timeFrame: 28 day
measure: time to weaning from mechanical ventilation
timeFrame: 28 days
measure: cumulative vasoactive-inotropic score (VIS)
timeFrame: 28 day
Other outcomes:
measure: adverse events
timeFrame: 28 day
measure: the ratio of ceftazidime plasma concentration to the pathogen's minimum inhibitory concentration (C/MIC)
timeFrame: 28 day
Locations:
Study officials:
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