Therapeutic Options for CRAB

NCT06440304 | Recruiting Phase 4 DMC

• 1 other identifier: CRAB01
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

CRAB infections in ICUs are on the rise, leading to higher morbidity, mortality, and healthcare costs due to resistance to most antibiotics, including carbapenems. The main resistance mechanisms include carbapenemases, efflux pumps, and changes in the bacterial cell wall. Current treatments include polymyxins (Colistin, Polymyxin B), which are effective but can lead to resistance, aminoglycosides (Amikacin, Gentamicin), which are limited by resistance, and tetracyclines (Tigecycline, Eravacycline), which are effective against CRAB. Fosfomycin is effective in combination treatments, and combination therapy (e.g., colistin with sulbactam, fosfomycin, or eravacycline) can enhance outcomes. Previous research shows promise for combination therapies, improving treatment efficacy and reducing mortality. New regimens are being studied to find optimal combinations. Individualized dosing is crucial, considering patient-specific factors like age, weight, and renal function. Adjustments depend on the infection site and comorbidities. Strict infection control and antimicrobial stewardship programs (ASPs) are essential. ASPs focus on optimizing antibiotic use and reducing resistance through education and surveillance. Future directions include continued research for new drugs or combinations and strategies to overcome resistance and improve treatment efficacy. Study goals include achieving negative samples after 10 days of therapy, 30-day survival, discharge rates, reduced SOFA scores, and improved clinical and radiological findings. A randomized study will compare colistin combined with fosfomycin, ampicillin/sulbactam, and eravacycline. In summary, treating CRAB infections is complex, requiring combination therapy, individualized dosing, and strict infection control measures.

Conditions

Infections, Bacterial; Sepsis Bacterial

Keywords

Carbapenem-resistant Acinetobacter baumannii (CRAB); Intensive Care Unit (ICU) infections; Polymyxins (colistin); Combination antimicrobial therapy; Antimicrobial resistance mechanisms; Fosfomycin; Eravacyclin; Ampicillin/sulbactam

Outcome Measures

Primary Outcomes (1)

• Negativisation

  Rate of negativisation of (surveillance or diagnostic) microbiological sample;

  10 days

Secondary Outcomes (3)

• Length of stay in ICU

  90 days

• Length of stay in hospital

  90 days

• Reduction of Sequential Organ Failure Assessment (SOFA) score

  10 days

Other Outcomes (2)

• 30 day Survival

  30 day

• Reduction of inflamatory parameters

  10 days

Study Arms (3)

Fosfomycin

ACTIVE COMPARATOR

Upon the detection of a positive microbiological finding for A. baumannii, the Fosfomycin group will receive 8 grams of fosfomycin every 8 hours, along with an initial colistin bolus of 6 million IU, followed by 3 million IU every 8 hours. After the first day, the dosage will be adjusted based on kidney and liver function. This therapy will be administered for a total of 10 days.

Drug: Fosfomycin

Ampicilin/sulbactam

ACTIVE COMPARATOR

Upon the detection of a positive microbiological finding for A. baumannii, the Ampicilin/sulbactam group will receive an initial bolus dose of 2 grams of ampicillin and 1 gram of sulbactam, followed by a continuous infusion of 8 grams of ampicillin and 4 grams of sulbactam over 24 hours (maximum daily dose of 12 grams per day), along with a colistin bolus of 6 million IU, followed by 3 million IU every 8 hours. After the first day, the dosage will be adjusted based on kidney and liver function. This therapy will be administered for a total of 10 days.

Drug: ampicillin/sulbactam

Eravacyclin

ACTIVE COMPARATOR

Upon the detection of a positive microbiological finding for A. baumannii, the Eravacyclin group will receive eravacycline at a dose of 1 mg/kg every 12 hours for 60 minutes, along with a colistin bolus of 6 million IU, followed by 3 million IU every 8 hours. After the first day, the dosage will be adjusted based on kidney and liver function. This therapy will be administered for a total of 10 days.

Drug: Eravacycline

Interventions

Fosfomycin DRUG

Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin

Also known as: Fosfomycin with Colistin

Fosfomycin

Eravacycline DRUG

Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin

Also known as: Eravacycline with Colistin

Eravacyclin

ampicillin/sulbactam DRUG

Patients will be randomly divided according to a predetermined randomization table Upon arrival of a positive microbiological finding on A. baumannii, patient will be randomised to one of groups (Colistin with Unasyn OR Colistin with Xerava OR Colistin with Fosfomycin

Also known as: Ampicilin/sulbactam with Colistin

Ampicilin/sulbactam

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Surgical patients (abdominal, vascular, and polytraumatized patients)
• Older than 18 years
• Require postoperative treatment in the ICU
• A positive sample (surveillance or diagnostic) for A. baumannii with signs of systemic infection
• Infection will be defined as a diagnostic microbiologically positive sample for A. baumannii and a surveillance microbiologically positive sample for A. baumannii with signs of systemic infection (elevated CRP, leukocytes, and body temperature).
• Colonization will be defined as a positive surveillance microbiological sample for A. baumannii in the absence of signs of systemic infection (normal CRP, leukocytes, and body temperature).

You may not qualify if:

• Allergy to the study medications
• Positive surveillance swabs for A. baumannii without signs of systemic infection
• Positive findings (surveillance or diagnostic) for carbapenem-sensitive A. baumannii
• Refusal to participate in the research

Sponsors & Collaborators

• Clinical Hospital Centre Zagreb: lead

Study Sites (1)

University Hospital Centre Zagreb

Zagreb, 10000, Croatia

RECRUITING

Related Publications (29)

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MeSH Terms

Conditions

Bacterial Infections; Infections

Interventions

Fosfomycin; Colistin; eravacycline; sultamicillin; Sulbactam

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; 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; Penicillins; beta-Lactams; Lactams; Amides; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ivan Šitum

  UHC Zagreb

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ivan Šitum

CONTACT

0915143620; ivsitum@gmail.com

Robert Baronica

CONTACT

0915143620; rbaronica@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal invesigator

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: June 3, 2024
• Study Start: January 30, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): February 1, 2027
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

CR (1)