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)

Infection Resistant to Multiple Drugs Clinical Trial

— LOKALE  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01894347
• Other study ID #: LOKALE
• Status: Completed
• Phase: N/A
• First received: July 1, 2013
• Last updated: August 2, 2016
• Start date: September 2013
• Est. completion date: December 2015

Study information

• Verified date: August 2016
• Source: Charite University, Berlin, Germany
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: December 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 (ß-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

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Infection Resistant to Multiple Drugs
• Neurotoxicity Syndromes
• Pneumonia
• Pneumonia, Ventilator-Associated

Intervention

Other:
• TDM, Monitoring of Neuro-and Nephropathology
Therapeutic drug monitoring of serum levels and Monitoring of Neuro- and Nephropathology

Locations

Country	Name	City	State
Germany	Charité Universitätsmedizin Charité	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany

Country where clinical trial is conducted

Germany, 

References & Publications (4)

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. — View 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. — View 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. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and frequency of adverse events (nephro- or neurotoxicity after aerosolised colistin therapy)	Adverse events are measured based on validated criteria: creatinine-clearance and RIFLE-criteria; Neuromonitoring (nerve conduction velocity, EEG)	28 days	Yes
Secondary	Serum concentration of colistin and ß-Lactam antibiotics	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	3 days	Yes
Secondary	Serum levels of colistin and ß-Lactam antibiotics (e.g. Meropenem)in mg/L	Serum drug levels in mg/L 2hours, 8 hours and 3 days (steady state) after therapy induction	3 days	Yes

External Links

•   This study initiative is launched by the ABx study group.