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) (LOKALE)

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Maria Deja, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier:
NCT01894347
First received: July 1, 2013
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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.


Condition Intervention
Infection Resistant to Multiple Drugs
Other: TDM, Monitoring of Neuro-and Nephropathology

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
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)

Resource links provided by NLM:


Further study details as provided by Charite University, Berlin, Germany:

Primary Outcome Measures:
  • Number and frequency of adverse events (nephro- or neurotoxicity after aerosolised colistin therapy) [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]

    Adverse events are measured based on validated criteria:

    1. creatinine-clearance and RIFLE-criteria
    2. Neuromonitoring (nerve conduction velocity, EEG)


Secondary Outcome Measures:
  • Serum concentration of colistin and β-Lactam antibiotics [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    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

  • Serum levels of colistin and β-Lactam antibiotics (e.g. Meropenem)in mg/L [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    Serum drug levels in mg/L 2hours, 8 hours and 3 days (steady state) after therapy induction


Biospecimen Retention:   Samples With DNA

Blood, tracheal aspirates


Estimated Enrollment: 12
Study Start Date: September 2013
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Colistin inhalative

Adult 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

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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Adult ICU patients with invasive ventilation and colonization or infection with MDR pathogens

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 pseudonymized data in context of the study
  • The patient is in an institution due to a court injunction or administrative order
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01894347

Locations
Germany
Charité Universitätsmedizin Charité
Berlin, Germany, 13353
Sponsors and Collaborators
Charite University, Berlin, Germany
Investigators
Principal Investigator: Maria Deja, Prof. Charité Universititaetsmedizin Berlin
  More Information

Additional Information:
Publications:
Responsible Party: Maria Deja, Prof. Dr. med. Maria Deja, Charite University, Berlin, Germany
ClinicalTrials.gov Identifier: NCT01894347     History of Changes
Other Study ID Numbers: LOKALE
Study First Received: July 1, 2013
Last Updated: March 31, 2014
Health Authority: Germany: Institutional Review Board

Keywords provided by Charite University, Berlin, Germany:
Colistin, MDR, inhalative therapy

Additional relevant MeSH terms:
Neurotoxicity Syndromes
Pneumonia, Ventilator-Associated
Cross Infection
Infection
Ventilator-Induced Lung Injury
Lung Injury
Lung Diseases
Respiratory Tract Diseases
Pneumonia
Respiratory Tract Infections
Nervous System Diseases
Poisoning
Chemically-Induced Disorders
Colistin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014