Clinical trial NCT02683603: Effect of Aerosolised Colistin in Ventilator Associated Pneumonia
Official title: Efficacy and Toxicity of Aerosolised Colistin in Ventilator Associated Pneumonia: A Prospective, Randomized Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Pneumonia, Ventilator-Associated
Keywords: colistin
aerosol
ventilator associated pneumonia
nephrotoxicity
intravenous
Lead sponsor: Tunis University
Sponsor class: OTHER
First posted: 2016-02-17
Enrollment: 133
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 management of Ventilator-associated pneumonia (VAP) caused by multidrug-resistant (MDR) gram-negative bacilli (GNB) represent a real therapeutic dilemma in intensive care unit (ICU). Colistin remains an effective agent against MDR GNB. However, because of its side effects, mainly nephrotoxicity, other modalities than the intra venous (IV) route should be tried. Several recent data emphasize the interest of inhaled route. The investigators purpose was to evaluate the effectiveness and systemic toxicity of aerosolized colistin in ventilator associated pneumonia.

Detailed description: prospective, randomized, single-blind study comparing two groups of patients treated with aerosolised (AS) colistin versus colistin intravenously (IV). Included were patients who have mechanical ventilation over 48 hours and that have developed a VAP. A VAP was defined as a CPIS (Clinical Pulmonary Infection Score) \>6. Exclusion criteria were septic shock and/or bacteraemia. Included patients were divided into two randomized groups. The 1st received colistin in AS as 4 MU by nebulisation 3 times per 24 h. The 2nd received colistin in IV as a loading dose of 9 MU followed by 4.5MU two times per 24 h. Colistin was given for 14 days or until extubation. Patients were followed for 28 days. Therapeutic efficacy was assessed by a primary outcome: the cure of VAP at day 14 of therapy and defined as resolution of clinical and biological signs of infection that means a CPIS\< 6 and bacteriological eradication. Secondary outcomes: duration of mechanical ventilation, ICU stay-length and mortality at day 28. Systemic toxicity was assessed by the occurrence of acute renal failure (ARF) defined as increase of plasma creatinine more than 1.5 times its base value.

Eligibility criteria: Inclusion Criteria:

* Critically ill patients older than 18 years, with mechanical ventilation during more than 48 hours, and who have presented a Ventilator associated Pneumonia (VAP) defined as a CPIS (Clinical Pulmonary Infection Score) of more than six

Exclusion Criteria:

* Age \<18 years
* Pregnancy
* Septic shock

Primary outcomes:
measure: cure of VAP
timeFrame: day 14 of therapy
Secondary outcomes:
measure: occurrence of acute renal failure
timeFrame: From date of randomization until the time of the cessation of colistin, assessed up 14 days on average
measure: duration of mechanical ventilation
timeFrame: From date of randomization until the time of weaning from ventilator, an average of 14 days
measure: length of stay in intensive unit
timeFrame: from randomisation until the time of patient discharge, an average of 28 days
Other outcomes:
measure: all cause mortality
timeFrame: 28 days
Locations:
city: Tunis
country: Tunisia
facility: intensive care unit of the University Hospital Center La Rabta
Study officials:
affiliation: Tunis University
name: Ahlem Trifi
role: STUDY_CHAIR
References:
citation: Abdellatif S, Trifi A, Daly F, Mahjoub K, Nasri R, Ben Lakhal S. Efficacy and toxicity of aerosolised colistin in ventilator-associated pneumonia: a prospective, randomised trial. Ann Intensive Care. 2016 Dec;6(1):26. doi: 10.1186/s13613-016-0127-7. Epub 2016 Mar 31.