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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)

Completed
Conditions
Infection Resistant to Multiple Drugs
Interventions
Other: TDM, Monitoring of Neuro-and Nephropathology
Registration Number
NCT01894347
Lead Sponsor
Charite University, Berlin, Germany
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
9
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Colistin inhalativeTDM, Monitoring of Neuro-and NephropathologyAdult ICU patients with * invasive ventilation 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 Patients included into the study group receive additional TDM, Monitoring of Neuro-and Nephropathology
Primary Outcome Measures
NameTimeMethod
Number and frequency of adverse events (nephro- or neurotoxicity after aerosolised colistin therapy)28 days

Adverse events are measured based on validated criteria:

1. creatinine-clearance and RIFLE-criteria

2. Neuromonitoring (nerve conduction velocity, EEG)

Secondary Outcome Measures
NameTimeMethod
Serum levels of colistin and β-Lactam antibiotics (e.g. Meropenem)in mg/L3 days

Serum drug levels in mg/L 2hours, 8 hours and 3 days (steady state) after therapy induction

Serum concentration of colistin and β-Lactam antibiotics3 days

Colistin-concentration in serum following inhalative therapy (in mg/L) 2 hours and 8 hours of application and in steady state on day 3 of therapy

Trial Locations

Locations (1)

Charité Universitätsmedizin Charité

🇩🇪

Berlin, Germany

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