Clinical trial NCT01894347: Prospective Observational Pilot-study for the Evaluation of the Nephro- an Neurotoxicity in the Anti-infectious Therapy With Inhalative Colistin Therapy for Patients With Ventilator-associated Pneumonia (VAP)
Official title: Prospective Observational Pilot-study for the Evaluation of the Nephro- an Neurotoxicity in the Anti-infectious Therapy With Inhalative Colistin Therapy for Patients With Ventilator-associated Pneumonia (VAP)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Infection Resistant to Multiple Drugs
Keywords: Colistin, MDR, inhalative therapy
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
First posted: 2013-07-10
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult ICU patients with invasive ventilation and colonization or infection with MDR pathogens

Brief summary: Multi-Drug resistant pathogens (MDR) are reported worldwide with increasing incidence, especially in intensive care settings.

One of the drugs which are effective against MDRs, is colistin (polymyxin E). This agent has been reintroduced in response to the increase of MDR pathogens and might be used more often in the future. Data on safety regarding the most important side effects are not sufficiently available. l This study evaluates the toxicity in patients who receive aerosolized colistin.

Detailed description: There is growing evidence that patients in the ICU setting have a special risk profile for consecutive colonization and possible infection due to MDR pathogens.

One therapy option is the use of inhalative colistin, as this agent has been demonstrated to be effective against these pathogens. Data on pharmacodynamics or - kinetics are transferred from older studies or from other patient populations. For patients with pulmonary colonization or infection due to an MDR pathogen the systemic resorption of the drug is not known, consequently systemic side effects including kidney or neural damage are not predictable.

This study focus on patients with inhalative colistin therapy and uses therapeutic drug monitoring to determine the rate of systemic resorption of colistin. For the evaluation of neurotoxicity function of peripheral nerves (neve conduction velocity) and of the eighth cranial nerve is monitored. Nephrotoxicity is estimated by creatinine level (-clearance) and the RIFLE criteria.

Eligibility criteria: Inclusion criteria:

* invasive ventilated patients (male and female) with assumed or assured bacteria with an elevated resistance pattern found in a tracheal or bronchial secretion with or without clinical signs of infection
* indicated colistin co-therapy or eradication-attempt with inhalative colistin (β-Lactam) therapy according to the standard operation procedure (SOP) of the hospital

Exclusion criteria:

* Consent of the patient or of the patient´s legal representative can´t be obtained soon
* Age \< 18 years
* Included within another, prospective clinical antibiotics-study
* Hypersensitivity to colistin or polymyxin B
* Patients with cystic fibrosis
* Present letter of attorney or patient´s provision, which precludes a priori the participation in studies
* Missing consent for storage of pseudonymised data in context of the study
* The patient is in an institution due to a court injunction or administrative order

Primary outcomes:
measure: Number and frequency of adverse events (nephro- or neurotoxicity after aerosolised colistin therapy)
timeFrame: 28 days
Secondary outcomes:
measure: Serum concentration of colistin and β-Lactam antibiotics
timeFrame: 3 days
measure: Serum levels of colistin and β-Lactam antibiotics (e.g. Meropenem)in mg/L
timeFrame: 3 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Charité
Study officials:
affiliation: Charité Universititaetsmedizin Berlin
name: Maria Deja, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Falagas ME, Siempos II, Rafailidis PI, Korbila IP, Ioannidou E, Michalopoulos A. Inhaled colistin as monotherapy for multidrug-resistant gram (-) nosocomial pneumonia: a case series. Respir Med. 2009 May;103(5):707-13. doi: 10.1016/j.rmed.2008.11.018. Epub 2008 Dec 31.
citation: Falagas ME, Rafailidis PI. Nephrotoxicity of colistin: new insight into an old antibiotic. Clin Infect Dis. 2009 Jun 15;48(12):1729-31. doi: 10.1086/599226. No abstract available.
citation: Michalopoulos AS, Karatza DC. Multidrug-resistant Gram-negative infections: the use of colistin. Expert Rev Anti Infect Ther. 2010 Sep;8(9):1009-17. doi: 10.1586/eri.10.88.
citation: Hamer DH. Treatment of nosocomial pneumonia and tracheobronchitis caused by multidrug-resistant Pseudomonas aeruginosa with aerosolized colistin. Am J Respir Crit Care Med. 2000 Jul;162(1):328-30. doi: 10.1164/ajrccm.162.1.9910071.