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Gram-Negative Bacterial InfectionsPhase 4NCT01732250

Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem

A Phase 4 study testing Colistin and Meropenem in people with Gram-Negative Bacterial Infections, run by Mical Paul at 7 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to determine whether the addition of meropenem to colistin is better than colistin alone in the treatment of clinically significant infections caused by multi-drug resistant bacteria Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Gram-Negative Bacterial Infections
What is being tested?
Colistin and Meropenem
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
406 participants
Where
7 sitesin 3 countries
Study dates
Mar 2013to 28 Feb 2017
Phase
Phase 4
Are there results?
None posted in the registry

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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult inpatients
  • Clinically significant, microbiological-documented infection caused by carbapenem-resistant and colistin-susceptible Gram-negative bacteria and identified according to CDC criteria- blood stream infections, hospital acquired pneumonia, ventilator associated pneumonia, and urinary tract infections
  • Patient recruitment will occur only after microbiological documentation and susceptibility testing. Patients will be included within 96 hours of the time the index culture was taken (typically within 48 hours of isolate identification), regardless of the antibiotic treatment administered during this time period.

Who cannot join

  • Previous inclusion in the trial. Patients will be included in the RCT only once for the first identified episode of infection
  • Pregnant women
  • Epilepsy or prior seizures
  • Known allergy to colistin or a carbapenem

Trial locations and contacts

7 sites in 3 countries.

7 sites in 3 countries

Israel3 sites

  • Rambam Health Care Center

    Haifa

  • Rabin Medical Center

    Petach-Tikvah

  • Tel-Aviv Sourasky Medical Center

    Tel Aviv

Other trials in Israel

Greece2 sites

  • Atikkon Hospital

    Athens

  • Laikon Hosptial

    Athens

Other trials in Greece

Italy2 sites

  • Monaldi Hospital, University of Naples S.U.N.

    Naples

  • Agostino Gemelli Hospital

    Rome

Other trials in Italy

About this study

Official title: Multicenter Open-label RCT to Compare Colistin Alone vs. Colistin Plus Meropenem

The purpose of this study is to determine whether the addition of meropenem to colistin is better than colistin alone in the treatment of clinically significant infections caused by multi-drug resistant bacteria

Being tested
Colistin, Meropenem
Keywords
Gram-Negative Bacterial Infections, Resistant Bacteria, Drug Resistance, Bacterial, Colistin
Medical subject headings
Gram-Negative Bacterial Infections

What participants receive

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

  • ColistinDrug

    Also called Colistimethate Sodium, Coliracin

    IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function, for 10 days.

  • MeropenemDrug

    Also called Meronem

    IV meropenem, 2 gram q8h, adjusted for renal function, for up to 10 days.

Study groups in NCT01732250
Study groupRoleWhat they receive
Colistin and MeropenemExperimentalIV meropenem, 2 gram q8h, adjusted for renal function IV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function
Receives: Drug: Colistin; Drug: Meropenem
ColistinActive comparatorIV Colistin with loading dose of 9 mil IU units, Maintenance dose 4.5 mil IU q12h, adjusted for renal function
Receives: Drug: Colistin

What is being measured

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

  1. Clinical success

    defined as a composite of all of the following, all measured at 14 days:

    • Patient alive
    • Systolic blood pressure >90 mmHg without need for vasopressor support
    • Stable or improved SOFA score, define as:
    • for baseline SOFA ≥ 3: a decrease of at least 30%;
    • for baseline SOFA <3: stable or decreased SOFA score
    • For patients with HAP/ VAP, PaO2/FiO2 ratio stable or improved
    • For patients with bacteremia, no growth of the initial isolate in blood cultures taken on day 14 if patient still febrile

    Measured: 14 days

Secondary outcomes (9)

  1. Secondary outcomes and adverse events

    14 and 28-day all-cause mortality.

    If patients are discharged or death occurs before end of follow-up (day 28), we will end data collection at that date. We will attempt to determine survival status at day 28 for all patients (central registry in Israel; re-admissions, rehabilitation centers, hospital transfers in Greece and Italy).

    Measured: 14 and 28 days

  2. Clinical success with modification

    Clinical success, but with modification to the antibiotic treatment not permitted by protocol

    Measured: 14 days

  3. Time to defervescence

    defined as time to reach a temperature of <38°C with no recurrence for 3 days

    Measured: 28 days

  4. Time to weaning

    Time to weaning from mechanical ventilation in VAP for patients weaned alive

    Measured: 28 days

  5. Time to hospital discharge

    Time to hospital discharge for patient discharged alive

    Measured: 28 days

  6. Microbiological failure

    Microbiological failure, defined as isolation of the initial isolate (phenotypically identical) in a clinical sample (blood or other) 7 days or more after start of treatment or its identification in respiratory samples.

    • For all patients with VAP/ HAP sputum or tracheal aspirates will be obtained on day 7, regardless of clinical response
    • For all patients with UTI, a repeat urine culture will be obtained on day 7, regardless of clinical response
    • For patients with bacteremia, blood cultures will be repeated on day 7 and 14, only if the patient is febrile at that time

    Measured: 28 days

  7. Superinfections

    Defined as a new clinically or microbiologically-documented infections by CDC criteria within 28 days

    Measured: 28 days

  8. New resistant infection

    Colonization or infection by newly-acquired (other species than the initial infection) carbapenem-resistant or colistin-resistant Gram-negative bacteria. Colonization will be assessed by rectal surveillance

    Measured: 28 days

  9. CDAD

    Clostridium-difficile-associated diarrhea, defined by diarrhea with a positive C. difficile toxin test

    Measured: 28 days

Timeline

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

  1. First posted22 Nov 2012 (estimated)
  2. Study startMar 2013
  3. Primary completion31 Jan 2017
  4. Study completion28 Feb 2017

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
None (open label)
Enrolment
406 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01732250
Sponsor's protocol ID
0276-12-RMC
Status last verified
Apr 2017
First submitted
19 Nov 2012
Last updated
12 Apr 2017
Results posted
No
Data monitoring committee
No

Publications

  • Nutman A, Temkin E, Lellouche J, Amar Ben Dalak M, Kaplan E, Lurie-Weinberger M, Dishon Benattar Y, Neuberger A, Stern A, Daitch V, Eliakim-Raz N, Durante-Mangoni E, Bernardo M, Iossa D, Daikos G, Skiada A, Pavleas I, Friberg L, Theuretzbacher U, Leibovici L, Paul M, Carmeli Y; AIDA Study Group. Carbapenem-resistant Enterobacterales (CRE) acquisition and molecular characterization following colistin monotherapy and colistin-meropenem combination therapy: findings from the AIDA randomized trial. Antimicrob Resist Infect Control. 2025 Nov 5;14(1):133. doi: 10.1186/s13756-025-01651-1.

    PubMed 41194117

  • Daitch V, 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, Cavezza G, Adler A, Dickstein Y, Pavleas I, Zampino R, Bitterman R, Zayyad H, Koppel F, Zak-Doron Y, Levi I, Babich T, Turjeman A, Ben-Zvi H, Friberg LE, Mouton JW, Theuretzbacher U, Leibovici L. Excluded versus included patients in a randomized controlled trial of infections caused by carbapenem-resistant Gram-negative bacteria: relevance to external validity. BMC Infect Dis. 2021 Mar 31;21(1):309. doi: 10.1186/s12879-021-05995-y.

    PubMed 33789574

  • Dickstein Y, Lellouche J, Ben Dalak Amar M, Schwartz D, Nutman A, Daitch V, Yahav D, Leibovici L, Skiada A, Antoniadou A, Daikos GL, Andini R, Zampino R, Durante-Mangoni E, Mouton JW, Friberg LE, Dishon Benattar Y, Bitterman R, Neuberger A, Carmeli Y, Paul M; AIDA Study Group. Treatment Outcomes of Colistin- and Carbapenem-resistant Acinetobacter baumannii Infections: An Exploratory Subgroup Analysis of a Randomized Clinical Trial. Clin Infect Dis. 2019 Aug 16;69(5):769-776. doi: 10.1093/cid/ciy988.

    PubMed 30462182

  • 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.

    PubMed 29456043

  • Dickstein Y, Leibovici L, Yahav D, Eliakim-Raz N, Daikos GL, Skiada A, Antoniadou A, Carmeli Y, Nutman A, Levi I, Adler A, Durante-Mangoni E, Andini R, Cavezza G, Mouton JW, Wijma RA, Theuretzbacher U, Friberg LE, Kristoffersson AN, Zusman O, Koppel F, Dishon Benattar Y, Altunin S, Paul M; AIDA consortium. Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol. BMJ Open. 2016 Apr 20;6(4):e009956. doi: 10.1136/bmjopen-2015-009956.

    PubMed 27098822

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Colistin and Meropenem in people with Gram-Negative Bacterial Infections, run by Mical Paul at 7 sites in 3 countries.

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 3 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: finished, as of the sponsor's last update on 12 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Israel, Greece, Italy. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Clinical success (time frame: 14 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 NCT01732250, which also lists 5 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 12 Apr 2017.

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