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

NCT01732250 | Completed Phase 4

• 1 other identifier: 0276-12-RMC
• Study Type: interventional
• Target: 406
• Locations: 3 countries
• Sites: 7

Brief 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

Conditions

Gram-Negative Bacterial Infections

Keywords

Gram-Negative Bacterial Infections; Resistant Bacteria; Drug Resistance, Bacterial; Colistin

Outcome Measures

Primary Outcomes (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

  14 days

Secondary Outcomes (9)

• Secondary outcomes and adverse events

  14 and 28 days

• Clinical success with modification

  14 days

• Time to defervescence

  28 days

• Time to weaning

  28 days

• Time to hospital discharge

  28 days

Study Arms (2)

Colistin and Meropenem

EXPERIMENTAL

IV 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

Drug: Colistin; Drug: Meropenem

Colistin

ACTIVE COMPARATOR

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

Drug: Colistin

Interventions

Colistin DRUG

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

Also known as: Colistimethate Sodium, Coliracin

Colistin; Colistin and Meropenem

Meropenem DRUG

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

Also known as: Meronem

Colistin and Meropenem

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Pregnant women
• Epilepsy or prior seizures
• Known allergy to colistin or a carbapenem

Sponsors & Collaborators

• Mical Paul: lead
• European Commission: collaborator

Study Sites (7)

Atikkon Hospital

Athens, Greece

Location

Laikon Hosptial

Athens, Greece

Location

Rambam Health Care Center

Haifa, Israel

Location

Rabin Medical Center

Petach-Tikvah, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

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

Naples, Italy

Location

Agostino Gemelli Hospital

Rome, Italy

Location

Related Publications (5)

• 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.

  PMID: 41194117 DERIVED

• 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.

  PMID: 33789574 DERIVED

• 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.

  PMID: 30462182 DERIVED

• 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 DERIVED

• 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.

  PMID: 27098822 DERIVED

MeSH Terms

Conditions

Gram-Negative Bacterial Infections

Interventions

Colistin; colistinmethanesulfonic acid; Meropenem

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

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; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Johan Mouton, MD PhD

  Radboud University Medical Center

  STUDY CHAIR

• Mical Paul, MD

  Rambam Health Care Centre

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 19, 2012
• First Posted: November 22, 2012
• Study Start: March 1, 2013
• Primary Completion: January 31, 2017
• Study Completion: February 28, 2017
• Last Updated: April 12, 2017

Record last verified: 2017-04

Locations

IL (3); GR (2); IT (2)