Therapeutic Options for CRAB (TheraCRAB)

January 16, 2026 updated by: Ivan Šitum, MD, Clinical Hospital Centre Zagreb

Therapeutic Strategies for Carbapenem-Resistant Acinetobacter Baumannii Infections: Study Protocol

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary goal will be to negativize positive samples (surveillance or diagnostic) after 10 days of therapy. In addition to the control samples with the same name, samples will be taken on the 4th, 7th, and 10th day after starting treatment.

The secondary objectives will include 30-day survival, discharge from the ICU, discharge from the hospital, reduction in SOFA score, rate of reinfection, and frequency of complications (deterioration of renal function). Reduction of CRP, PCT, and leukocytes, improvement of the clinical picture, improvement of radiological findings (such as X-ray of the lungs), and reduction of elevated body temperature will also be included.

Patients who require treatment in the ICU with a positive sample (surveillance or diagnostic) for A. baumannii, with clinical signs of infection (temperature >38.5, CPR >50, L >10000) (in which no infection can be explained by another cause) will be included.

Three groups will be formed:

  1. colistin + fosfomycin
  2. colistin + ampicilin/sulbactam
  3. colistin + eravacyclin

The outcomes will include a negative sample, length of stay in the ICU, length of stay in the hospital, and reduction of SOFA score.

The hypothesis will be that the combination of fosfomycin with colistin and eravacyclin with colistin will lead to faster negative samples than the combination of ampicillin/sulbactam with colistin in intensive care unit patients diagnosed with carbapenem-resistant A. baumannii.

After obtaining approval from the ethics committee of KBC Zagreb, this study will be conducted at the UHC Zagreb, Department of Anesthesiology and ICU. Patients will be randomly divided according to a predetermined randomization table.

Upon arrival of a positive microbiological finding on A. baumannii, the Fosfomycin group will receive fosfomycin 8 g every 8 h, together with a colistin bolus of 6 million IJ, followed by 3 million IJ every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be administered for 10 days.

Upon arrival of a positive microbiological finding on A. baumannii, the Ampicilin/sulbactam group will receive a bolus dose of ampicillin/sulbactam 2 g + 1 g and a continuous infusion of 8 g + 4 g over 24 h together (maximum daily dose 12 g/day) with a colistin bolus of 6 million IJ, followed by 3 million IJ every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be performed for 10 days.

Upon arrival of a positive microbiological finding for A. baumannii, the Eravacyclin group will receive eravacycline at a dose of 1 mg/kg every 12 h for 60 min together with a colistin bolus of 6 million IU, and then 3 million IU every 8 h. After the first day, the dose will be adjusted according to kidney and liver function. Therapy will be administered for 10 days.

After the first positive microbiological finding for A. baumannii, the test will be repeated on the 4th, 7th, and 10th days from the start of therapy. The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study. The SOFA score will be calculated daily for each patient over 10 days.

Patient data from a hospital information system will be used in this study. Demographic data, comorbidities, habits (alcohol and cigarettes), Charlson comorbidity index, SOFA score, allergies, and the type of positive sample will be recorded. The Charlson Comorbidity Index will be calculated for each patient upon inclusion in the study. The SOFA score will be calculated daily for each patient over 10 days. Patients will be included in the study after the arrival of a microbiological test positive for A. baumannii. A routine antimicrobial susceptibility test will be performed when the microbiological findings are positive for A. baumannii. The sensitivity of all A. baumannii strains included in the study, regardless of the group to which they belonged (fosfomycin, ampicilin/sulbactam, and eravacyclin), will be determined during the microbiological analysis of all A. baumannii strains included in the study. After the first positive microbiological finding for A. baumannii, the test will be repeated on the 3th, 7th, and 10th days from the start of therapy. For each patient included in the study, inflammatory parameters (leukocytes, CRP, procalcitonin) and the number of days and discharge from the ICU and hospital as well as 30-day mortality and cause of death, complications (AKI and ALF), and reinfection will be monitored.

For a test power of 80% and the use of an independent t-test for the primary objective and a chi-square test for the secondary objective with a statistical significance of 0.05, it will be necessary to include 108 patients, divided into three groups, with 36 subjects per group. The test for power calculation will be conducted using G Power Version 3.1.9.6. The results will be processed using IBM SPSS Statistics v27.

Study Type

Interventional

Enrollment (Estimated)

108

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Croatia
      • Zagreb, Croatia, 10000
        • Recruiting
        • University Hospital Centre Zagreb
        • Contact:
        • Principal Investigator:
          • Ivan Šitum
        • Contact:
          • Robert Baronica
        • Principal Investigator:
          • Robert Baronica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Fosfomycin
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
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
Other Names:
  • Fosfomycin with Colistin
Active Comparator: Ampicilin/sulbactam
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
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
Other Names:
  • Ampicilin/sulbactam with Colistin
Active Comparator: Eravacyclin
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
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
Other Names:
  • Eravacycline with Colistin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Negativisation
Time Frame: 10 days
Rate of negativisation of (surveillance or diagnostic) microbiological sample;
10 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Length of stay in ICU
Time Frame: 90 days
Days spent in ICU total after randomisation
90 days
Length of stay in hospital
Time Frame: 90 days
Days spent in hospital total after randomisation
90 days
Reduction of Sequential Organ Failure Assessment (SOFA) score
Time Frame: 10 days
Change in initial SOFA score from randomisation day, from 0 points to 24
10 days

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
30 day Survival
Time Frame: 30 day
patients survived 30 days after randomisation
30 day
Reduction of inflamatory parameters
Time Frame: 10 days
Reduction of parameters of inflamation (L,CRP, PCT)
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Clinical Hospital Centre Zagreb

Investigators

  • Principal Investigator: Ivan Šitum, UHC Zagreb

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 30, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

May 21, 2024

First Submitted That Met QC Criteria

May 27, 2024

First Posted (Actual)

June 3, 2024

Study Record Updates

Last Update Posted (Actual)

January 21, 2026

Last Update Submitted That Met QC Criteria

January 16, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRAB01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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