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Clinical Trial NCT05922124 (CASCADE) for Carbapenem Resistant Bacterial Infection, Acinetobacter Bacteremia, Acinetobacter Pneumonia is recruiting. See the Trial Radar Card View and AI discovery tools for all the details. Or ask anything here.
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Cefiderocol and Ampicillin-sulbactam vs. Colistin +/- Meropenem for Carbapenem Resistant A. Baumannii (CASCADE) Phase 4 734

Recruiting
Clinical Trial NCT05922124 (CASCADE) is designed to study Treatment for Carbapenem Resistant Bacterial Infection, Acinetobacter Bacteremia, Acinetobacter Pneumonia. It is a Phase 4 interventional study that is recruiting, having started on 1 September 2024, with plans to enroll 734 participants. Led by Rambam Health Care Campus, it is expected to complete by 1 September 2026. The latest data from ClinicalTrials.gov was last updated on 1 August 2025.
Brief Summary
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.
Detailed Description
This will be a prospective controlled clinical study with historical controls.

In the prospective CASCADE study consecutive consenting patients with bloodstream infections, hospital acquired pneumonia or ventilator-associated pneumonia will be treated with cefiderocol combined with ampicillin sulbactam in 3 hospitals in Israel and 2 hospitals in Italy, all endemic for CRAB. We plan to recruit 150 patients into this ...

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Official Title

Cefiderocol and Ampicillin-sulbactam vs. Colistin or Colistin-meropenem for Carbapenem Resistant Acinetobacter Baumannii Bacteremia or Hospital-acquired Pneumonia: Controlled Clinical Study With Historical Controls (CASCADE)

Conditions
Carbapenem Resistant Bacterial InfectionAcinetobacter BacteremiaAcinetobacter Pneumonia
Publications
Scientific articles and research papers published about this clinical trial:
Other Study IDs
  • CASCADE
  • V0.1 May 2023
NCT ID Number
NCT05922124
Start Date (Actual)
2024-09-01
Last Update Posted
2025-08-01
Completion Date (Estimated)
2026-09
Enrollment (Estimated)
734
Study Type
Interventional
PHASE
Phase 4
Status
Recruiting
Primary Purpose
Treatment
Design Allocation
Non-Randomized
Interventional Model
Parallel
Masking
None (Open Label)
Arms / Interventions
Participant Group/ArmIntervention/Treatment
ExperimentalCefiderocol + ampicillin-sulbactam
Cefiderocol 2 gram intravenous (IV) q8 hours and ampicillin-sulbactam 3 gram IV q6 hours for patients with normal creatinine clearance, both administered as extended infusion of 3 hours. Dosing adjusted according to reduced and augmented renal clearance and to renal replacement therapies.
Cefiderocol
Test drug regimen
Ampicillin-sulbactam
Synergistic combination
Active ComparatorColistin or colistin + meropenem
Colistin 9 million units (MIU) intravenous (IV) loading dose followed by 4.5 MIU for patients with normal creatinine clearance +/- meropenem 2 gram IV administered as extended infusion of 3 hours. Dosing adjusted according to reduced and augmented renal clearance and to renal replacement therapies.
Colistin
Historical comparator
Meropenem
Historical comparator synergistic combination
Primary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
All cause mortality
Death from any cause
28 days
Secondary Outcome Measures
Outcome MeasureMeasure DescriptionTime Frame
All cause mortality
Death from any cause
14 days
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
Day 10-14
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.
Day 5-7
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
28 days
Hospital stay
Among 28-day survivors
28 days
Decline in functional capacity
Functional capacity will be assessed in four categories: independent; requires some assistance; requires assistance for activities of daily living (ADL); and bedridden. Decline in functional capacity will be defined as any 1-category worsening.
28 days
Adverse event - Clostridiodes difficile infection
Diarrhea with a positive C. difficile toxin test
28 days
Adverse event - renal failure
Renal failure due to any reason using the RIFLE ( risk, injury, failure, loss, End stage kidney disease) criteria (classifying patients to None, Risk, Injury, Failure, Loss and ESRD) at day 14 and day 28 and defined as worsening by two RIFLE categories (e.g. from Risk to Failure, etc.)
28 days
Adverse event - Acute liver injury
Increase in aspartate aminotransferase (AST) or alanine transaminase (ALT) \> 3-fold or increased bilirubin \>2 above upper limits of normal (ULN) or baseline value if higher than ULN.
28 days
Participation Assistant
Eligibility Criteria

Eligible Ages
Child, Adult, Older Adult
Minimum Age
16 Years
Eligible Sexes
All

Adults >18 years with bacteremia or hospital-acquired pneumonia (HAP)/ ventilator-associated pneumonia (VAP) (Table 3) caused by carbapenem-resistant A. baumannii (CRAB) (meropenem and/ or imipenem minimal inhibitory concentration (MIC) >8 μg/mL) susceptible to cefiderocol (disc zone diameter >=17 mm, corresponding to an MIC <2 μg/mL). We will include CRAB regardless of colistin, ampicillin-sulbactam, minocycline, tigecycline, trimethoprim/sulfamethoxazole and/or aminoglycoside susceptibility of the isolate. Attribution of the HAP/ VAP to CRAB will be allowed with isolation of CRAB from any respiratory sample within 7 days prior to the clinical diagnosis of pneumonia.

  • 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
  • Immediate-type hypersensitivity to penicillin
  • Pregnant women
  • Previous participation in the trial
  • Lack of informed consent, considering the procedures acceptable to ethics committees per locale, including deferred consent
  • Infection requiring treatment for over 14 days, at the discretion of the investigators
  • Life expectancy less than 24 hours or expected futility of antibiotic treatment
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Study Central Contact
Contact: Mical Paul, 0502062140, [email protected]
Contact: Marco Falcone, [email protected]
3 Study Locations in 1 Countries
Rambam Health Care Campus, Haifa, Israel
Mical Paul, MD, Contact, [email protected]
Mical Paul, MD, Principal Investigator
Recruiting
Sheba Tel HaShomer Medical Campus, Ramat Gan, Israel
Dafna Dahav, MD, Contact
Dafna Yahav, MD, Principal Investigator
Recruiting
Shamir Medical Center (Assaf Harofeh), Tel Aviv, Israel
Dror Marchaim, Contact
Recruiting