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CONTinuous Infusion Versus Intermittent Dosing of ceftaZidime/AVIbactam in Critically Ill Patients

ConditionSevere Infection
Trial statusNot yet recruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18-85
SponsorIvan Šitum, MD

About this trial

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

This trial does not accept healthy volunteers

Qualifiers

General

Age above or equal to 18 years of age.

Able to provide informed consent personally or by his/her next of kin, as requested by the Ethics Committee.

Disease-specific

Disqualifiers

General

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).

Withdrawal of informed consent.

Age above 85 years of age.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Continuos ceftazidime/avibactam infusion

    Drug

    Continuous infusion will include a loading dose of 2 g/0.5 g administered over 2 hours, followed by continuous infusion of 6 g/1.5 g over 24 hours, equivalent to 0.25 g of ceftazidime per hour. The drug reconstitution and dilution process are shown in Figure 2. The final volume of solution of CZA will be 50 mL, which gives concentration of ceftazidime of 40 mg/mL, with 4:1 concentration ratio for avibactam (10 mg/mL). The solution will be administered via an infusion syringe, with an infusion rate of 6.25 mL/h. Dose adjustments will be applied according to renal function, calculated using Cockroft-Gault formula

  • Intermitent dosing as per SMPC

    Drug

    Intermittent dosing, as outlined in the SmPC, consists of 2 g/0.5 g administered by prolonged infusion over 2 hours every 8 hours. Dose adjustments will be applied according to renal function, calculated using Cockroft-Gault formula.

Treatment groups

140 Participants
are divided into 2 treatment groups
Group A: Continuos ceftazidime/avibactam infusionExperimental treatment 1 intervention
Group B: Intermitent dosing as per SMPCActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

microbiological success rate

The aim of this study is to investigate efficacy of continuous infusion of ceftazidime/avibactam compared to conventional intermittent dosing, in treating critically ill ICU patients with severe infections caused by Klebsiella pneumoniae OXA-48 or Pseudomonas aeruginosa. The primary outcome of the study is microbiological success rate, defined by proportion of patients in whom the causative pathogen is absent from specimen at the site of infection.

Time frame
28 days

Secondary outcomes

1

clinical success rate

The clinical success rate is the proportion of patients who achieve clinical cure or clinical improvement evaluated at the end of therapy. Clinical cure is the complete resolution of all signs and symptoms, with no evidence of ongoing infection. Clinical improvement is a significant reduction in infection-related signs and symptoms such that the patient demonstrates considerable progress towards recovery.

Time frame
28 day
2

time to symptoms improvement

Patients who achieve clinical cure or clinical improvement

Time frame
28 day
3

length of ICU stay

Length of ICU stay is defined as the total number of days from the day of the first CZA administration (study day on 0) until either: Discharge from the ICU (if the patient is transferred out of the ICU before day 28) Day 28 (for patients who remain in the ICU beyond this time)

Time frame
28 day
4

length of hospital stay

Length of hospital stay is defined as the total number of days from the day of the first CZA administration (study day on 0) until either: Discharge from the hospital (if the patient is discharged before day 28) Day 28 (for patients who remain hospitalized beyond this time)

Time frame
28 day

Other outcomes

1

adverse events

Any adverse event that can be attributed to ceftazidime/avibactam

Time frame
28 day
2

the ratio of ceftazidime plasma concentration to the pathogen's minimum inhibitory concentration (C/MIC)

The ratio of ceftazidime plasma concentration to the pathogen's minimum inhibitory concentration (C/MIC).

Time frame
28 day

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ivan Šitum, MD

Lead sponsor

Clinical Hospital Centre Zagreb

Sponsor institution

UHC Zagreb, Zagreb, Croatia

Collaborator

Daniel Lovrić

Collaborator

Mirna Momčilović

Collaborator

Source ClinicalTrials.gov

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