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Severe InfectionPhase 4ZAVICONTNCT06811727

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

A Phase 4 study testing Continuos ceftazidime/avibactam infusion and Intermitent dosing as per SMPC in people with Severe Infection, run by Ivan Šitum, MD at 1 site in Croatia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Severe Infection
What is being tested?
Continuos ceftazidime/avibactam infusion and Intermitent dosing as per SMPC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
1 siteCroatia
Study dates
1 Aug 2025to 1 Aug 2029
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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.
  • Female who is pregnant or breast-feeding.
  • 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.
Show all 14Show fewer
  • Any disorder which, in the investigator's opinion, might jeopardize the participant's safety or compliance with the protocol.
  • Laboratory values
  • 1. Severe neutropenia before or during ceftazidime/avibactam administration.
  • Medical conditions
  • Death within 48 hours following randomization.
  • Concomitant acquired immunodeficiency syndrome.
  • Presence or history of malignant neoplasms or in situ carcinomas.
  • Duration of ceftazidime/avibactam administration is shorter than 72 hours.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ivan Šitum, MD contact

0915143620

ivsitum@gmail.com

Daniel Lovrić, MD, PhD contact

385914488350

daniel@lovric.net

Croatia1 site, 1 recruiting
  • UHC ZAgreb

    Zagreb, 10000

    Daniel Lovrić, assist. prof., 0914488350, daniel@dlovric.net

    Recruiting

Other trials in Croatia

About this study

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)

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).

Read more

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.

Being tested
Continuos ceftazidime/avibactam infusion, Intermitent dosing as per SMPC
Keywords
ceftazidime/avibactam, continuous infusion, critically ill, ICU, Klebsiella pneumoniae OXA-48, Pseudomonas aeruginosa
Medical subject headings
Infections, Critical Illness, Pseudomonas Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Continuos ceftazidime/avibactam infusionDrug

    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 SMPCDrug

    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.

Study groups in NCT06811727
Study groupRoleWhat they receive
Continuos ceftazidime/avibactam infusionExperimentalContinuous 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 a solution of CZA will be 50 mL, which gives the concentration of ceftazidime 40 mg/mL, with a 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 the Cockroft-Gault formula
Receives: Drug: Continuos ceftazidime/avibactam infusion
Intermitent dosing as per SMPCActive comparatorIntermittent 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 the Cockroft-Gault formula.
Receives: Drug: Intermitent dosing as per SMPC

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 28 days

Secondary outcomes (8)
  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.

    Measured: 28 day

  2. time to symptoms improvement

    Patients who achieve clinical cure or clinical improvement

    Measured: 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)

    Measured: 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)

    Measured: 28 day

  5. all-cause 28-day mortality after ceftazidime/avibactam initiation

    All-cause 28-day mortality is defined as death at any point up to and including study day 28. The 28-day mortality rate will be calculated as the number of deaths divided by the total number of patients in the group, expressed as a percentage.

    Measured: 28 day

  6. pathogen recurrence rate on day 28

    The pathogen recurrence rate on day 28 is defined as the proportion of patients who have a recurrence of the initial causative pathogen from clinical or surveillance microbiological samples taken by study day 28 after completion of CZA therapy.

    Measured: 28 day

  7. time to weaning from mechanical ventilation

    time in hours from the start of the trial to the end of mechanical ventilation

    Measured: 28 days

  8. cumulative vasoactive-inotropic score (VIS)

    The vasoactive-inotropic score is a quantitative measure that evaluates the cumulative effect of vasoactive and inotropic medications. It is calculated using the following formula:

    VIS = dobutamine dose (μg/kg/min) + adrenaline dose (μg/kg/min) x 100 + noradrenaline dose (μg/kg/min) x 100 + vasopressin dose (IU/kg/min) x 10 + angiotensin II dose (ng/kg/min) x 10000 24-hour VIS quantifies the overall cardiovascular support required over 24 hours. The average daily VIS score will be calculated using the following formula: Daily VIS=∑ (VIS for each interval × interval duration (hours)/24 An interval is defined as the period where drug doses remain constant.

    Measured: 28 day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Feb 2025
  2. Study start1 Aug 2025
  3. Primary completion1 May 2029 (estimated)
  4. Study completion1 Aug 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
140 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06811727
Sponsor's protocol ID
ZAVICONT01
Acronym
ZAVICONT
Status last verified
Oct 2026
First submitted
28 Jan 2025
Last updated
2 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007 May;39(2):175-91. doi: 10.3758/bf03193146.

    PubMed 17695343
  • Servais H, Tulkens PM. Stability and compatibility of ceftazidime administered by continuous infusion to intensive care patients. Antimicrob Agents Chemother. 2001 Sep;45(9):2643-7. doi: 10.1128/AAC.45.9.2643-2647.2001.

    PubMed 11502544
  • Gatti M, Pea F. Continuous versus intermittent infusion of antibiotics in Gram-negative multidrug-resistant infections. Curr Opin Infect Dis. 2021 Dec 1;34(6):737-747. doi: 10.1097/QCO.0000000000000755.

    PubMed 34261906
  • Adembri C, Novelli A, Nobili S. Some Suggestions from PK/PD Principles to Contain Resistance in the Clinical Setting-Focus on ICU Patients and Gram-Negative Strains. Antibiotics (Basel). 2020 Oct 6;9(10):676. doi: 10.3390/antibiotics9100676.

    PubMed 33036190
  • Lorente L, Jimenez A, Palmero S, Jimenez JJ, Iribarren JL, Santana M, Martin MM, Mora ML. Comparison of clinical cure rates in adults with ventilator-associated pneumonia treated with intravenous ceftazidime administered by continuous or intermittent infusion: a retrospective, nonrandomized, open-label, historical chart review. Clin Ther. 2007 Nov;29(11):2433-9. doi: 10.1016/j.clinthera.2007.11.003.

    PubMed 18158083
  • Gomez CM, Cordingly JJ, Palazzo MG. Altered pharmacokinetics of ceftazidime in critically ill patients. Antimicrob Agents Chemother. 1999 Jul;43(7):1798-802. doi: 10.1128/AAC.43.7.1798.

    PubMed 10390248
  • Muller AE, Punt N, Mouton JW. Optimal exposures of ceftazidime predict the probability of microbiological and clinical outcome in the treatment of nosocomial pneumonia. J Antimicrob Chemother. 2013 Apr;68(4):900-6. doi: 10.1093/jac/dks468. Epub 2012 Nov 28.

    PubMed 23190766
  • Ali A, Imran M, Sial S, Khan A. Effective antibiotic dosing in the presence of resistant strains. PLoS One. 2022 Oct 10;17(10):e0275762. doi: 10.1371/journal.pone.0275762. eCollection 2022.

    PubMed 36215219
  • Ghazi IM, El Nekidy WS. Editorial: Advances in antimicrobial therapy and combating resistance. Front Pharmacol. 2023 Mar 16;14:1170289. doi: 10.3389/fphar.2023.1170289. eCollection 2023. No abstract available.

    PubMed 37007043
  • Batchelder JI, Hare PJ, Mok WWK. Resistance-resistant antibacterial treatment strategies. Front Antibiot. 2023;2:1093156. doi: 10.3389/frabi.2023.1093156. Epub 2023 Jan 30.

    PubMed 36845830
  • Poole K. Pseudomonas aeruginosa: resistance to the max. Front Microbiol. 2011 Apr 5;2:65. doi: 10.3389/fmicb.2011.00065. eCollection 2011.

    PubMed 21747788
  • Bonomo RA, Burd EM, Conly J, Limbago BM, Poirel L, Segre JA, Westblade LF. Carbapenemase-Producing Organisms: A Global Scourge. Clin Infect Dis. 2018 Apr 3;66(8):1290-1297. doi: 10.1093/cid/cix893.

    PubMed 29165604
  • Chen T, Xu H, Chen Y, Ji J, Ying C, Liu Z, Xu H, Zhou K, Xiao Y, Shen P. Identification and Characterization of OXA-232-Producing Sequence Type 231 Multidrug Resistant Klebsiella pneumoniae Strains Causing Bloodstream Infections in China. Microbiol Spectr. 2023 Apr 13;11(2):e0260722. doi: 10.1128/spectrum.02607-22. Epub 2023 Mar 22.

    PubMed 36946763
  • Garcia-Gonzalez N, Fuster B, Tormo N, Salvador C, Gimeno C, Gonzalez-Candelas F. Genomic analysis of the initial dissemination of carbapenem-resistant Klebsiella pneumoniae clones in a tertiary hospital. Microb Genom. 2023 Jun;9(6):mgen001032. doi: 10.1099/mgen.0.001032.

    PubMed 37272914
  • Ceron S, Salem-Bango Z, Contreras DA, Ranson EL, Yang S. Clinical and Genomic Characterization of Carbapenem-Resistant Klebsiella pneumoniae with Concurrent Production of NDM and OXA-48-like Carbapenemases in Southern California, 2016-2022. Microorganisms. 2023 Jun 30;11(7):1717. doi: 10.3390/microorganisms11071717.

    PubMed 37512889

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Continuos ceftazidime/avibactam infusion and Intermitent dosing as per SMPC in people with Severe Infection, run by Ivan Šitum, MD at 1 site in Croatia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ivan Šitum, MD (0915143620, ivsitum@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

microbiological success rate (time frame: 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06811727, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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