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Cefiderocol and Ampicillin-sulbactam vs. Colistin +/- Meropenem for Carbapenem Resistant A. Baumannii

ConditionsCarbapenem Resistant Bacterial InfectionAcinetobacter BacteremiaAcinetobacter Pneumonia
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age16+
SponsorRambam Health Care Campus

About this trial

Patients with bloodstream infections, hospital acquired pneumonia or ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii (CRAB) treated with cefiderocol combined with ampicillin sulbactam will be compared to patients treated treated with colistin alone or colistin combined with meropenem.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

None

Disqualifiers

More than 72 hours of therapy with in-vitro coverage against the CRAB within 96 hours of enrolment

Polymicrobial carbapenem-susceptible infections: growth of other pathogens susceptible to carbapenems, or another beta-lactam, deemed clinically-significant by the treating physicians in blood or sputum (with HAP/ VAP). We will allow recruitment of patients with other carbapenem-resistant Gram-negative bacteria

CRAB susceptible any beta-lactam other than cefiderocol

Coronavirus 2019 (COVID-19) co-infection

Trial design

Design model

Parallel

Treatments tested in this trial

  • Cefiderocol

    Drug

    Test drug regimen

  • Ampicillin-sulbactam

    Drug

    Synergistic combination

  • Colistin

    Drug

    Historical comparator

  • Meropenem

    Drug

    Historical comparator synergistic combination

Treatment groups

734 Participants
are divided into 2 treatment groups
Group A: Cefiderocol + ampicillin-sulbactamExperimental treatment 2 interventions
Group B: Colistin or colistin + meropenemActive comparator 2 interventions

Trial outcomes

Primary outcomes

1

All cause mortality

Death from any cause

Time frame
28 days

Secondary outcomes

1

All cause mortality

Death from any cause

Time frame
14 days
2

Clinical failure

Composite of: * Death * Systolic blood pressure ≤90 mmHg or need for vasopressor support * Worsening sequential organ failure assessment score (SOFA) score, define as: * for baseline SOFA ≥ 3: stable or increased * for baseline SOFA \<3: any increase * For patients with hospital-acquired pneumonia (HAP)/ ventilator-associated pneumonia (VAP), partial pressure of oxygen in arterial blood (PaO2)/ fraction of inspired oxygen (FiO2) ratio worsened * For patients with bacteremia, growth of the initial isolate in blood cultures after ≥ 5 days since study treatment start

Time frame
Day 10-14
3

Microbiological failure

Isolation of the initial isolate (phenotypically identical) in blood cultures 5 days or more after start of treatment or in respiratory samples 7 days or more.

Time frame
Day 5-7
4

Resistance development to cefiderocol

Development of carbapenemase-producing Enterobacterales (CPE), non-CPE carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant A. baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) resistance to cefiderocol in clinical and surveillance cultures collected as defined in the study's protocol

Time frame
28 days

Other outcomes

1

Desirability of Outcome Ranking (DOOR)

Defined DOOR outcome analysis: Alive no event; Alive 1 event; Alive 2 events; Alive 3 events; Dead. The DOOR events will be: (1) Clinical failure as defined above (2) Hospital stay \>14 days from enrolment (3) Adverse events: renal failure, Clostridiodes difficile infection or acute liver injury

Time frame
28 days

Sponsors and contacts

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

Rambam Health Care Campus

Lead sponsor

Monaldi Hospital

Collaborator

Rutgers Robert Wood Johnson Medical School

Collaborator

Pisa University Hospital

Collaborator

Assaf-Harofeh Medical Center

Collaborator

Sheba Medical Center

Collaborator

Source ClinicalTrials.gov
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