Effect of Aerosolised Colistin in Ventilator Associated Pneumonia

February 16, 2016 updated by: Ahlem Trifi, Tunis University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

133

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Tunisia
      • Tunis, Tunisia, 1007
        • intensive care unit of the University Hospital Center La Rabta

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: aerosolised (AS) colistin group
the intervention was: AS colistin and "imipenem. the drug administered was colimycin (colistin) powder 1 million units (MU) by a flakon (Sanofi Winthrop Industry) at the dosage of 4 million units (MU) for 30 minutes 3 times per day for at least 14 days in addition to IV imipenem 1 g three times per day. Nebulisation was made via an ultrasonic vibrating plates nebulizer (Aeroneb Pro® Aerogen Nektar Corporation, Galway, Ireland). Inhaled colimycin® requires specific settings of the ventilator to limit turbulence inspiratory flow. The adjustment consisted in a volume controlled mode with a Tidal volume <8 ml / kg, respiratory rate at 12 cycles / min, I / E: 1/1 and an end inspiratory break > 20%.
Drug: AS colistin and "imipenem"
colimycin (colistin) powder (1 million units (MU) by flakon) by AS route in addition to imipenem
Other Names:
  • colimycin (colistin) powder (Sanofi laboratories)
Drug: 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).
Other Names:
  • colimycin (colistin)
Drug: AS colistin and imipenem
IV imipenem 1 g three times per day.
Other Names:
  • imipenem
Active Comparator: intravenous (IV) colistin goup
the intervention was: IV colistin and "imipenem. the intravenous (IV) colistin goup received IV colimycin (colistin) as a loading dose of 9 MU during 60 minutes followed by 4.5 million units 2 times per day in addition to IV imipenem 1 g three times per day.
Drug: IV colistin " and "imipenem" .
colimycin (colistin) powder (1 MU by flakon) by intravenous route in addition to imipenem
Other Names:
  • colimycin (colistin) powder (Sanofi laboratories)
Drug: IV colimycin (colistin)
intravenous colimycin (colistin) : 9 MU during 60 minutes followed by 4.5 million units 2 times per day
Other Names:
  • colimycin (colistin) powder by intravenous route
Drug: IV colistin and imipenem
IV imipenem 1 g three times per day
Other Names:
  • imipenem

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
cure of VAP
Time Frame: day 14 of therapy
a CPIS (clinical pulmonary infection score) less than 6 and bacterial eradication
day 14 of therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
occurrence of acute renal failure
Time Frame: From date of randomization until the time of the cessation of colistin, assessed up 14 days on average
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
duration of mechanical ventilation
Time Frame: From date of randomization until the time of weaning from ventilator, an average of 14 days
From date of randomization until the time of weaning from ventilator, an average of 14 days
length of stay in intensive unit
Time Frame: from randomisation until the time of patient discharge, an average of 28 days
from randomisation until the time of patient discharge, an average of 28 days

Other Outcome Measures

Outcome Measure
Time Frame
all cause mortality
Time Frame: 28 days
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tunis University

Investigators

  • Study Chair: Ahlem Trifi, Tunis University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2013

Primary Completion (Actual)

April 1, 2015

Study Completion (Actual)

April 1, 2015

Study Registration Dates

First Submitted

February 5, 2016

First Submitted That Met QC Criteria

February 16, 2016

First Posted (Estimate)

February 17, 2016

Study Record Updates

Last Update Posted (Estimate)

February 17, 2016

Last Update Submitted That Met QC Criteria

February 16, 2016

Last Verified

February 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Tunis university

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

yes of course the data is collected on individual cards which identified demographic, clinical and laboratory data for each patient participating. thereafter these data is entered on Statistical Package for Social Sciences (SPSS) software

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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