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Carbapenem-Resistant Enterobacteriaceae InfectionPhase 3AVI-ICUNCT05258851

Ceftazidime-Avibactam Use in Critically Ill Patients With Carbapenem-Resistant Enterobacteriaceae Infections

A Phase 3 study testing Ceftazidime-avibactam and Colistin in people with Carbapenem-Resistant Enterobacteriaceae Infection, run by King Faisal Specialist Hospital & Research Center at 1 site in Saudi Arabia.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Carbapenem-Resistant Enterobacteriaceae (CRE) infections are a growing national and international challenge in healthcare settings. This is not only due to the rapid spread of resistance and paucity of options of targeted-antimicrobial agents, but also owing to the high mortality of patients infected with CRE reaching… Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Ceftazidime-avibactam and Colistin
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
29 participants
Where
1 siteSaudi Arabia
Study dates
1 Jun 2022to 28 Jan 2024
Phase
Phase 3
Are there results?
None posted in the registry

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

  • Patients aged ≥ 18 years.
  • Admitted to an intensive care unit (ICU).
  • Patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), complicated urinary tract infection (cUTI), bacteremia, complicated intraabdominal infection (cIAI), and complicated skin and soft tissue infection (cSSTI).
  • Confirmed infection with CRE, based on a culture and sensitivity obtained within the past 72 hours of study enrollment.
  • Suspected CRE infection according to one of the following: (1) positive Xpert Carba-R test screening for blaKPC or blaOXA-48 or blaNDM or blaVIM or blaIMI assessed on the admission to the ICU, (2) positive culture for CRE obtained within 3 months from time of enrollment.

Who cannot join

  • Acute Physiology and Chronic Health Evaluation II (APACHE II) score more than 30
  • known significant hypersensitivity reaction to beta-lactam antibiotics or colistin
  • Positive culture for Stenotrophomonas maltophilia or Acinetobacter baumannii within the current hospitalization.
  • Patients received the study intervention or control for more than 24 hours before the intended randomization.
  • Patient/substitute decision-maker or caring physician's refusal to enroll in the study.
  • Patient with concomitant suspected or confirmed meningitis.
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  • Pregnancy.
  • Cystic fibrosis.
  • Patients with Do Not Attempt to Resuscitate (DNAR) code status.
  • Prior knowledge that the index CRE pathogen was resistant to colistin (MIC >2 μg/ml) or ceftazidime-avibactam (MIC > 8 μg/ml) before randomization.
  • Objective clinical evidence for any of the following infections that necessitate study therapy for >14 days: endovascular infection, including endocarditis, osteomyelitis, prosthetic joint infection, meningitis, and/or other central nervous system infections

Trial locations and contacts

1 site in 1 country.

Saudi Arabia1 site

  • King Faisal Specialist Hospital & Research Centre

    Riyadh

Other trials in Saudi Arabia

About this study

Official title: Ceftazidime-Avibactam Versus Colistin in Critically Ill Patients With Carbapenem-Resistant Enterobacteriaceae Infections (AVI-ICU): A Non-Inferiority Randomized Clinical Trial

Carbapenem-Resistant Enterobacteriaceae (CRE) infections are a growing national and international challenge in healthcare settings. This is not only due to the rapid spread of resistance and paucity of options of targeted-antimicrobial agents, but also owing to the high mortality of patients infected with CRE reaching up to 50% as per the Centers of Disease Control and Prevention.

Colistin-based combination regimens have been the mainstay for treating CRE-related infections. Ceftazidime-avibactam is a beta-lactamase inhibitor combination, a novel antibiotic, which recently showed a better clinical and microbiological cure against CRE along with the potential to reduce mortality and nephrotoxicity in comparison to colistin-based regimens in observational studies. However, randomized clinical trials are lacking.

This non-inferiority randomized controlled study aims to assess the efficacy and safety of ceftazidime-avibactam-based regimens in critically ill patients with CRE infections in comparison to colistin-based regimens.

Being tested
Ceftazidime-avibactam, Colistin
Keywords
Carbapenem-Resistant Enterobacteriaceae, Critically ill, Ceftazidime-avibactam, Colistin
Medical subject headings
Critical Illness

What participants receive

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

  • Ceftazidime-avibactamDrug

    Experimental

  • ColistinDrug

    Control

Study groups in NCT05258851
Study groupRoleWhat they receive
Ceftazidime-avibactamExperimentalCeftazidime-avibactam 2.5 grams intravenous (IV) every 8 hours infused over two hours for a duration of 7-14 days, with dose adjustment for renal impairment according to the FDA prescribing information. Patients who have a positive Xpert Carb-R screening test or culture for CRE with metallo-beta-lactamases will receive aztreonam added to ceftazidime-avibactam.
Receives: Drug: Ceftazidime-avibactam
ColistinActive comparatorColistin (9-million-unit loading dose IV followed with 9 million units IV daily divided into 3 doses), for 7 to 14 days. Patients with renal impairment will receive antibiotics with adjusted doses based on their glomerular filtration rate or the use and type of renal replacement therapy according to the 2019 International Consensus Guidelines for the Optimal Use of the Polymyxins.
Receives: Drug: Colistin

What is being measured

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

  1. 28-day mortality

    Death

    Measured: 28 days from randomization

Secondary outcomes (8)

  1. 14-day mortality

    Death

    Measured: 14 days from randomization

  2. Number of patients with clinical success at end of therapy (EOT) at day 7-14 from randomization and test of cure (TOC) 7 days after completion of treatment

    Defined as:

    1- Alive, fever or hypothermia resolution, WBC counts normalization, hemodynamic stability with MAP ≥65 mmHg without vasopressors support.

    1. For HAP or VAP: 1+ improving respiratory status including improving PaO2/FiO2 ratio from baseline, decreasing FiO2 and PEEP or extubation or source control for empyema.
    2. For bloodstream infection: 1+ documented two negative blood cultures with source removal if applicable.
    3. For complicated intra-abdominal infection: 1+ resolution or decreasing size of intra-abdominal collections with source control if applicable.
    4. For complicated skin and soft tissue infection: 1+ resolution of signs and symptoms plus surgical drainage or debridement if applicable.
    5. For complicated urinary tract infection: 1+ resolution of signs and symptoms and source removal if applicable.

    Measured: EOT at 7-14 days from randomization and TOC 7 days after completion of treatment

  3. Number of patients with microbiological response at the EOT at days 7-14 from randomization and TOC 7 days after completion of treatment

    Defined as:

    1. Eradication (successful microbiological response): Baseline pathogen no longer present in the culture(s) that indicated the use of study drugs.
    2. Presumed eradication (successful microbiological response): Patient deemed a clinical cure as assessed by the adjudication committee at EOT and TOC, and repeat culture that indicated enrollment in the study is not available.
    3. Persistence (failure of microbiological response): Presence of baseline pathogen in the culture that indicated the use of study drugs.
    4. Presumed persistence (failure of microbiological response): Patients deemed a clinical failure as assessed by the adjudication committee at EOT and TOC, and specimen is not available.
    5. Indeterminate: Any culture that cannot be classified into one of the above categories, or the patient was an indeterminate clinical response and no cultures were taken.

    Measured: EOT at 7-14 days from randomization and TOC 7 days after completion of treatment

  4. Time to weaning from mechanical ventilation at day 28

    Number of days not receiving mechanical ventilation

    Measured: 28 days from randomization

  5. Requirement for renal replacement therapy at day 28

    New start of renal replacement therapy

    Measured: 28 days from randomization

  6. Intensive care unit (ICU) length of stay, censored at 28 days

    Duration of stay inside the ICU

    Measured: 28 days from randomization

  7. Days alive and out of the ICU, censored at 28 days

    Number of days alive and outside the ICU

    Measured: 28 days from randomization

  8. Drug-related adverse events

    Acute kidney injury, seizures, leukopenia, thrombocytopenia, allergic reaction, diarrhea, clostridium difficile infection.

    Measured: 28 days from randomization

Timeline

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

  1. First posted28 Feb 2022
  2. Study start1 Jun 2022
  3. Primary completion12 Apr 2023
  4. Study completion28 Jan 2024

Why it stopped: Difficulties encountered in the recruitment process and slow enrollment. The study was not terminated due to any safety issues or concerns.

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
Open-label, multicenter, parallel-group, stratified, non-inferiority randomized controlled trial
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
29 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05258851
Sponsor's protocol ID
RAC#2211247
Acronym
AVI-ICU
Status last verified
Jun 2024
First submitted
17 Feb 2022
Last updated
14 Jun 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ceftazidime-avibactam and Colistin in people with Carbapenem-Resistant Enterobacteriaceae Infection, run by King Faisal Specialist Hospital & Research Center at 1 site in Saudi Arabia.

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 5 inclusion and 11 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: stopped early, as of the sponsor's last update on 14 Jun 2024. 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 Saudi Arabia. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

The study was stopped early (reason given: Difficulties encountered in the recruitment process and slow enrollment. The study was not terminated due to any safety issues or concerns.). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

28-day mortality (time frame: 28 days from randomization). 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 NCT05258851.

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 14 Jun 2024.

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AVI-ICU Clinical Trial NCT05258851 | AzTrials