Effect of Aerosolised Colistin in Ventilator Associated Pneumonia

Pneumonia, Ventilator-Associated Clinical Trial

Official title:

Efficacy and Toxicity of Aerosolised Colistin in Ventilator Associated Pneumonia: A Prospective, Randomized Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02683603
• Other study ID #: Tunis university
• Status: Completed
• Phase: Phase 4
• First received: February 5, 2016
• Last updated: February 16, 2016
• Start date: April 2013
• Est. completion date: April 2015

Study information

• Verified date: February 2016
• Source: Tunis University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Tunisia: Office of Pharmacies and Medicines
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pneumonia
• Pneumonia, Ventilator-Associated

Intervention

Drug:
• AS colistin and "imipenem"
colimycin (colistin) powder (1 million units (MU) by flakon) by AS route in addition to imipenem
• IV colistin " and "imipenem" .
colimycin (colistin) powder (1 MU by flakon) by intravenous route in addition to imipenem
• AS colimycin (colistin)
nebulisation of colimycin (colistin) for 30 minutes 3 times per day during at least 14 days. Nebulisation was made via an ultrasonic vibrating plates nebulizer (Aeroneb Pro® Aerogen Nektar Corporation, Galway, Ireland).
• IV colimycin (colistin)
intravenous colimycin (colistin) : 9 MU during 60 minutes followed by 4.5 million units 2 times per day
• AS colistin and imipenem
IV imipenem 1 g three times per day.
• IV colistin and imipenem
IV imipenem 1 g three times per day

Locations

Country	Name	City	State
Tunisia	intensive care unit of the University Hospital Center La Rabta	Tunis

Sponsors (1)

Lead Sponsor	Collaborator
Tunis University

Country where clinical trial is conducted

Tunisia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	all cause mortality		28 days	No
Primary	cure of VAP	a CPIS (clinical pulmonary infection score) less than 6 and bacterial eradication	day 14 of therapy	No
Secondary	occurrence of acute renal failure	an acute renal failure was defined as increase of plasma creatinine more than 1.5 times its base value.	From date of randomization until the time of the cessation of colistin, assessed up 14 days on average	No
Secondary	duration of mechanical ventilation		From date of randomization until the time of weaning from ventilator, an average of 14 days	No
Secondary	length of stay in intensive unit		from randomisation until the time of patient discharge, an average of 28 days	No