TY - JOUR
T1 - 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)
T2 - A study protocol
AU - Dickstein, Yaakov
AU - Leibovici, Leonard
AU - Yahav, Dafna
AU - Eliakim-Raz, Noa
AU - Daikos, George L.
AU - Skiada, Anna
AU - Antoniadou, Anastasia
AU - Carmeli, Yehuda
AU - Nutman, Amir
AU - Levi, Inbar
AU - Adler, Amos
AU - Durante-Mangoni, Emanuele
AU - Andini, Roberto
AU - Cavezza, Giusi
AU - Mouton, Johan W.
AU - Awijma, Rixt
AU - Theuretzbacher, Ursula
AU - Friberg, Lena E.
AU - Kristoffersson, Anders N.
AU - Zusman, Oren
AU - Koppel, Fidi
AU - Benattar, Yael Dishon
AU - Altunin, Sergey
AU - Paul, Mical
PY - 2016
Y1 - 2016
N2 - Mical Paul,1,14 Introduction: The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification. Methods and analysis: This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gramnegative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilatorassociated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patientswho met eligibility requirements but were not randomised in order to assess generalisability of findings. Ethics and dissemination: The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.
AB - Mical Paul,1,14 Introduction: The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification. Methods and analysis: This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin-meropenem combination therapy for infections caused by carbapenem-resistant Gramnegative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilatorassociated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patientswho met eligibility requirements but were not randomised in order to assess generalisability of findings. Ethics and dissemination: The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The trial is being performed under the auspices of an independent data and safety monitoring committee and is included in a broad dissemination strategy regarding revival of old antibiotics.
UR - http://www.scopus.com/inward/record.url?scp=84971277787&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2015-009956
DO - 10.1136/bmjopen-2015-009956
M3 - Article
C2 - 27098822
AN - SCOPUS:84971277787
SN - 2044-6055
VL - 6
JO - BMJ Open
JF - BMJ Open
IS - 4
M1 - e009956
ER -
