Clinical trial NCT01732250: Multicenter Open-label Randomized Controlled Trial (RCT) to Compare Colistin Alone Versus Colistin Plus Meropenem
Official title: Multicenter Open-label RCT to Compare Colistin Alone vs. Colistin Plus Meropenem
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gram-Negative Bacterial Infections
Keywords: Gram-Negative Bacterial Infections
Resistant Bacteria
Drug Resistance, Bacterial
Colistin
Lead sponsor: Rabin Medical Center
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2012-11-22
Enrollment: 406
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Clinical success
timeFrame: 14 days
Secondary outcomes:
measure: Secondary outcomes and adverse events
timeFrame: 14 and 28 days
measure: Clinical success with modification
timeFrame: 14 days
measure: Time to defervescence
timeFrame: 28 days
measure: Time to weaning
timeFrame: 28 days
measure: Time to hospital discharge
timeFrame: 28 days
measure: Microbiological failure
timeFrame: 28 days
measure: Superinfections
timeFrame: 28 days
measure: New resistant infection
timeFrame: 28 days
measure: CDAD
timeFrame: 28 days
Other outcomes:
Locations:
city: Athens
country: Greece
facility: Atikkon Hospital
city: Athens
country: Greece
facility: Laikon Hosptial
city: Haifa
country: Israel
facility: Rambam Health Care Center
city: Petach-Tikvah
country: Israel
facility: Rabin Medical Center
city: Tel-Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Naples
country: Italy
facility: Monaldi Hospital, University of Naples S.U.N.
city: Rome
country: Italy
facility: Agostino Gemelli Hospital
Study officials:
affiliation: Radboud University Medical Center
name: Johan Mouton, MD PhD
role: STUDY_CHAIR
affiliation: Rambam Health Care Centre
name: Mical Paul, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.