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

NCT05922124 | Recruiting Phase 4 FDA Drug

• 1 other identifier: V0.1 May 2023
• Study Type: interventional
• Target: 734
• Locations: 1 country
• Sites: 3

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.

Conditions

Carbapenem Resistant Bacterial Infection; Acinetobacter Bacteremia; Acinetobacter Pneumonia

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  Death from any cause

  28 days

Secondary Outcomes (9)

• All cause mortality

  14 days

• Clinical failure

  Day 10-14

• Microbiological failure

  Day 5-7

• Resistance development to cefiderocol

  28 days

• Hospital stay

  28 days

Other Outcomes (1)

• Desirability of Outcome Ranking (DOOR)

  28 days

Study Arms (2)

Cefiderocol + ampicillin-sulbactam

EXPERIMENTAL

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.

Drug: Cefiderocol; Drug: Ampicillin-sulbactam

Colistin or colistin + meropenem

ACTIVE COMPARATOR

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.

Drug: Colistin; Drug: Meropenem

Interventions

Cefiderocol DRUG

Test drug regimen

Also known as: Fetroja

Cefiderocol + ampicillin-sulbactam

Ampicillin-sulbactam DRUG

Synergistic combination

Also known as: Unasyn

Cefiderocol + ampicillin-sulbactam

Colistin DRUG

Historical comparator

Colistin or colistin + meropenem

Meropenem DRUG

Historical comparator synergistic combination

Colistin or colistin + meropenem

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Rambam Health Care Campus: lead
• Monaldi Hospital: collaborator
• Rutgers Robert Wood Johnson Medical School: collaborator
• Pisa University Hospital: collaborator
• Assaf-Harofeh Medical Center: collaborator
• Sheba Medical Center: collaborator

Study Sites (3)

Rambam Health Care Campus

Haifa, Israel

RECRUITING

Sheba Tel HaShomer Medical Campus

Ramat Gan, Israel

RECRUITING

Shamir Medical Center (Assaf Harofeh)

Tel Aviv, Israel

RECRUITING

Related Publications (2)

• Paul M, Daikos GL, Durante-Mangoni E, Yahav D, Carmeli Y, Benattar YD, Skiada A, Andini R, Eliakim-Raz N, Nutman A, Zusman O, Antoniadou A, Pafundi PC, Adler A, Dickstein Y, Pavleas I, Zampino R, Daitch V, Bitterman R, Zayyad H, Koppel F, Levi I, Babich T, Friberg LE, Mouton JW, Theuretzbacher U, Leibovici L. Colistin alone versus colistin plus meropenem for treatment of severe infections caused by carbapenem-resistant Gram-negative bacteria: an open-label, randomised controlled trial. Lancet Infect Dis. 2018 Apr;18(4):391-400. doi: 10.1016/S1473-3099(18)30099-9. Epub 2018 Feb 16.

  PMID: 29456043 BACKGROUND

• Kaye KS, Marchaim D, Thamlikitkul V, Carmeli Y, Chiu CH, Daikos G, Dhar S, Durante-Mangoni E, Gikas A, Kotanidou A, Paul M, Roilides E, Rybak M, Samarkos M, Sims M, Tancheva D, Tsiodras S, Kett D, Patel G, Calfee D, Leibovici L, Power L, Munoz-Price S, Stevenson K, Susick L, Latack K, Daniel J, Chiou C, Divine GW, Ghazyaran V, Pogue JM. Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms. NEJM Evid. 2023 Jan;2(1):10.1056/evidoa2200131. doi: 10.1056/evidoa2200131. Epub 2022 Dec 6.

  PMID: 37538951 BACKGROUND

MeSH Terms

Interventions

Cefiderocol; sultamicillin; Colistin; Meropenem

Intervention Hierarchy (Ancestors)

Cephalosporins; beta-Lactams; Lactams; Amides; Organic Chemicals; Thiazines; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins; Thienamycins; Carbapenems

Study Officials

• Marco Falcone

  Pisa University Hospital

  PRINCIPAL INVESTIGATOR

• Dafna Yahav

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

• Mical Paul

  Rambam Health Care Campus

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mical Paul

CONTACT

0502062140; paulm@technion.ac.il

Marco Falcone

CONTACT

marco.falcone@unipi.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Controlled clinical study with historical controls

Study Record Dates

• First Submitted: May 31, 2023
• First Posted: June 28, 2023
• Study Start: September 1, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 1, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: As soon as published
• Access Criteria: Justification to lead author

Locations

IL (3)