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Infections, BacterialPhase 4TheraCRABNCT06440304

Therapeutic Options for CRAB

A Phase 4 study testing Fosfomycin, Eravacycline and ampicillin/sulbactam in people with Infections, Bacterial and Sepsis Bacterial, run by Clinical Hospital Centre Zagreb at 1 site in Croatia.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Infections, Bacterial, Sepsis Bacterial
What is being tested?
Fosfomycin, Eravacycline and ampicillin/sulbactam
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
108 participants
Where
1 siteCroatia
Study dates
30 Jan 2025to Feb 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ivan Šitum contact

0915143620

ivsitum@gmail.com

Robert Baronica contact

0915143620

rbaronica@gmail.com

Croatia1 site, 1 recruiting

  • University Hospital Centre Zagreb

    Zagreb, 10000

    Ivan Šitum, 0915143620, ivsitum@gmail.com

    Robert Baronica

    Recruiting

Other trials in Croatia

About this study

Official title: 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.

Read more

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.

Read the 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.

Being tested
Fosfomycin, Eravacycline, ampicillin/sulbactam
Keywords
Carbapenem-resistant Acinetobacter baumannii (CRAB), Intensive Care Unit (ICU) infections, Polymyxins (colistin), Combination antimicrobial therapy, Antimicrobial resistance mechanisms, Fosfomycin, Eravacyclin, Ampicillin/sulbactam
Medical subject headings
Bacterial Infections, Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • FosfomycinDrug

    Also called Fosfomycin with Colistin

    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

  • EravacyclineDrug

    Also called Eravacycline with Colistin

    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

  • ampicillin/sulbactamDrug

    Also called Ampicilin/sulbactam with Colistin

    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

Study groups in NCT06440304
Study groupRoleWhat they receive
FosfomycinActive comparatorUpon 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.
Receives: Drug: Fosfomycin
Ampicilin/sulbactamActive comparatorUpon 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.
Receives: Drug: ampicillin/sulbactam
EravacyclinActive comparatorUpon 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.
Receives: Drug: Eravacycline

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Negativisation

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

    Measured: 10 days

Secondary outcomes (3)

  1. Length of stay in ICU

    Days spent in ICU total after randomisation

    Measured: 90 days

  2. Length of stay in hospital

    Days spent in hospital total after randomisation

    Measured: 90 days

  3. Reduction of Sequential Organ Failure Assessment (SOFA) score

    Change in initial SOFA score from randomisation day, from 0 points to 24

    Measured: 10 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jun 2024
  2. Study start30 Jan 2025
  3. Primary completionDec 2026 (estimated)
  4. Study completionFeb 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
108 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06440304
Sponsor's protocol ID
CRAB01
Acronym
TheraCRAB
Status last verified
Jan 2026
First submitted
21 May 2024
Last updated
21 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Šitum I, Mamić G, Džaja N, Hrvoić L, Lovrić D, Siroglavić M, et al. Upala pluća povezana s mehaničkom ventilacijom uzrokovana bakterijom Acinetobacter baumannii u razdoblju pandemije COVID-19. Medicina Fluminensis : Medicina Fluminensis [Internet]. 2023 Jun 1 [cited 2024 Apr 30];59(2):139-48. Available from: http://hrcak.srce.hr/medicinamedicinafluminensis

  • Carbapenem-resistant Acinetobacter baumannii (CRAB): An urgent public health threat in United States healthcare facilities | A.R. & Patient Safety Portal [Internet]. [cited 2024 May 2]. Available from: https://arpsp.cdc.gov/story/cra-urgent-public-health-threat

  • Shields RK, Paterson DL, Tamma PD. Navigating Available Treatment Options for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections. Clin Infect Dis. 2023 May 1;76(Suppl 2):S179-S193. doi: 10.1093/cid/ciad094.

    PubMed 37125467

  • Isler B, Doi Y, Bonomo RA, Paterson DL. New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections. Antimicrob Agents Chemother. 2018 Dec 21;63(1):e01110-18. doi: 10.1128/AAC.01110-18. Print 2019 Jan.

    PubMed 30323035

  • Viehman JA, Nguyen MH, Doi Y. Treatment options for carbapenem-resistant and extensively drug-resistant Acinetobacter baumannii infections. Drugs. 2014 Aug;74(12):1315-33. doi: 10.1007/s40265-014-0267-8.

    PubMed 25091170

  • Dalfino L, Stufano M, Bavaro DF, Diella L, Belati A, Stolfa S, Romanelli F, Ronga L, Di Mussi R, Murgolo F, Loconsole D, Chironna M, Mosca A, Montagna MT, Saracino A, Grasso S. Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study. Antibiotics (Basel). 2023 Jun 14;12(6):1048. doi: 10.3390/antibiotics12061048.

    PubMed 37370367

  • Paul M, Carrara E, Retamar P, Tangden T, Bitterman R, Bonomo RA, de Waele J, Daikos GL, Akova M, Harbarth S, Pulcini C, Garnacho-Montero J, Seme K, Tumbarello M, Lindemann PC, Gandra S, Yu Y, Bassetti M, Mouton JW, Tacconelli E, Rodriguez-Bano J. European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the treatment of infections caused by multidrug-resistant Gram-negative bacilli (endorsed by European society of intensive care medicine). Clin Microbiol Infect. 2022 Apr;28(4):521-547. doi: 10.1016/j.cmi.2021.11.025. Epub 2021 Dec 16.

    PubMed 34923128

  • Rodrigues RD, Garcia RCL, Bittencourt GA, Waichel VB, Garcia ECL, Rigatto MH. Antimicrobial Therapy Duration for Bloodstream Infections Caused by Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex: A Retrospective Cohort Study. Antibiotics (Basel). 2023 Mar 8;12(3):538. doi: 10.3390/antibiotics12030538.

    PubMed 36978405

  • Reina R, Leon-Moya C, Garnacho-Montero J. Treatment of Acinetobacter baumannii severe infections. Med Intensiva (Engl Ed). 2022 Dec;46(12):700-710. doi: 10.1016/j.medine.2022.08.007. Epub 2022 Oct 19.

    PubMed 36272902

  • Acinetobacter in Healthcare Settings | HAI | CDC [Internet]. [cited 2024 Apr 30]. Available from: https://www.cdc.gov/hai/organisms/acinetobacter.html

  • Nartey YA, Donkor AB, Siaw ADJ, Ekor OE, Jimah BB. Carbapenem-Resistant Acinetobacter baumannii Bloodstream Infection in a Ghanaian Patient with Unilateral Diaphragmatic Eventration and HIV Type 1 Infection. Case Rep Infect Dis. 2023 Oct 12;2023:9930291. doi: 10.1155/2023/9930291. eCollection 2023.

    PubMed 37867582

  • Kim SH, Wi YM, Peck KR. Clinical Effectiveness of Tetracycline-Class Agents Based Regimens in Patients With Carbapenem-Resistant Acinetobacter baumannii Bacteremia: A Single-Center Retrospective Cohort Study. J Korean Med Sci. 2023 Aug 28;38(34):e263. doi: 10.3346/jkms.2023.38.e263.

    PubMed 37644679

  • Jung SY, Lee SH, Lee SY, Yang S, Noh H, Chung EK, Lee JI. Antimicrobials for the treatment of drug-resistant Acinetobacter baumannii pneumonia in critically ill patients: a systemic review and Bayesian network meta-analysis. Crit Care. 2017 Dec 20;21(1):319. doi: 10.1186/s13054-017-1916-6.

    PubMed 29262831

  • Pogue JM, Zhou Y, Kanakamedala H, Cai B. Burden of illness in carbapenem-resistant Acinetobacter baumannii infections in US hospitals between 2014 and 2019. BMC Infect Dis. 2022 Jan 6;22(1):36. doi: 10.1186/s12879-021-07024-4.

    PubMed 34991499

  • Seok H, Choi WS, Lee S, Moon C, Park DW, Song JY, Cheong HJ, Kim J, Kim JY, Park MN, Kim YR, Lee HJ, Kim B, Pai H, Jo YM, Kim JH, Sohn JW. What is the optimal antibiotic treatment strategy for carbapenem-resistant Acinetobacter baumannii (CRAB)? A multicentre study in Korea. J Glob Antimicrob Resist. 2021 Mar;24:429-439. doi: 10.1016/j.jgar.2021.01.018. Epub 2021 Feb 8.

    PubMed 33571708

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Fosfomycin, Eravacycline and ampicillin/sulbactam in people with Infections, Bacterial and Sepsis Bacterial, run by Clinical Hospital Centre Zagreb at 1 site in Croatia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ivan Šitum (0915143620, ivsitum@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Negativisation (time frame: 10 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06440304, which also lists 29 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jan 2026.

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