Infection Resistant to Multiple DrugsLOKALENCT01894347
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)
An observational study of Infection Resistant to Multiple Drugs, run by Charite University, Berlin, Germany at 1 site in Germany.
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Infection Resistant to Multiple Drugs
- What is being tested?
- TDM, Monitoring of Neuro-and Nephropathology
- How many people
- 9 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2013to Dec 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult ICU patients with invasive ventilation and colonization or infection with MDR pathogens
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Charité Universitätsmedizin Charité
Berlin, State of Berlin, 13353
About this study
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.
Read the 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.
- Conditions
- Infection Resistant to Multiple Drugs
- Being tested
- TDM, Monitoring of Neuro-and Nephropathology
- Keywords
- Colistin, MDR, inhalative therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TDM, Monitoring of Neuro-and NephropathologyOther
Therapeutic drug monitoring of serum levels and Monitoring of Neuro- and Nephropathology
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Other: TDM, Monitoring of Neuro-and Nephropathology |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 28 days
Secondary outcomes (2)
Serum concentration of colistin and β-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
Measured: 3 days
Serum levels of colistin and β-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
Measured: 3 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startSep 2013
- Primary completionApr 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Infection Resistant to Multiple DrugsStudies of the same condition, open and under way.
- More trials run by Charite University, Berlin, GermanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Charite University, Berlin, Germany
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maria Deja, Charite University, Berlin, Germany
- Investigators
- Maria Deja, Prof., Principal investigator, Charité Universititaetsmedizin Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01894347
- Sponsor's protocol ID
- LOKALE
- Acronym
- LOKALE
- Status last verified
- Aug 2016
- First submitted
- 1 Jul 2013
- Last updated
- 3 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19118994Falagas 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.
PubMed 19438398Michalopoulos 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.
PubMed 20818945Hamer 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.
PubMed 10903263
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01894347
- Acronym / sponsor ID
- LOKALE / LOKALE
- Conditions
- Infection Resistant to Multiple Drugs
- Keywords
- Colistin, MDR, inhalative therapy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Charite University, Berlin, GermanyUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Apr 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 10 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Colistin inhalative | – | Other: TDM, 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult ICU patients with invasive ventilation and colonization or infection with MDR pathogens
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TDM, Monitoring of Neuro-and NephropathologyTherapeutic drug monitoring of serum levels and Monitoring of Neuro- and Nephropathology | Other | Colistin inhalative |
Primary outcome
Number and frequency of adverse events (nephro- or neurotoxicity after aerosolised colistin therapy)
Time frame: 28 days
Adverse events are measured based on validated criteria: 1. creatinine-clearance and RIFLE-criteria 2. Neuromonitoring (nerve conduction velocity, EEG)
2 secondary outcomes
Serum concentration of colistin and β-Lactam antibiotics
Time frame: 3 days
Serum levels of colistin and β-Lactam antibiotics (e.g. Meropenem)in mg/L
Time frame: 3 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2016.
- Background: PubMed 19118994Falagas 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.
- Background: PubMed 19438398Falagas 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.
- Background: PubMed 20818945Michalopoulos 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.
- Background: PubMed 10903263Hamer 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.
- This study initiative is launched by the ABx study group.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Maria Deja, Prof. principal investigator
Charité Universititaetsmedizin Berlin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infection Resistant to Multiple Drugs, run by Charite University, Berlin, Germany at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and frequency of adverse events (nephro- or neurotoxicity after aerosolised colistin therapy) (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01894347, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2016.