- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02482961
Impact of Plasma Levels of Colistin in Patients With Carbapenem Resistant Acinetobacter Baumannii Infection
Prospective Observational Study, Impact of Plasma Levels of Colistin in Patients With Carbapenem Resistant Acinetobacter Baumannii Infection
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Acinetobacter baumanii usually causes pneumonia and sepsis, and is susceptible to antibiotics such as ampicillin/sulbactam and carbapenem, but it easily becomes tolerant and there are few other drugs usable. Particularly in Korean patients with ventilator-associated pneumonia (VAP), the percentage of carbapenem-resistant Acinetobacter baumannii (CRAB) is increasing recently.
Colistin (polymyxin E) is antibiotic of polymyxin line used to multidrug-resistant gram-negative bacteria such as Klebsiella pneumonia, Pseudomonas aeruginosa, and Acinetobacter baumannii, and it produces bactericidal action by destroying bacterial cell membrane. Colistin was antibiotic isolated from Bacillius polymyxa subspecies colistinus first in Japan in 1949, and has long been used in clinic since 1959, but its use through intravenous infusion decreased in the 1970s due to acute kidney injury and neurotoxicity. Recently, however, it is being used more frequently for hospital infection by multidrug-resistant gram-negative bacteria and, as a result, various studies are being conducted on colistin.
Colistin consists of over 30 different polymyxin compounds including colistin A (polymyxin E1) and colistin B (polymyxin E2), and colistimethate sodium (CMS) and colistin sulfate are used. In Korea, it is usually administered intravenously in the form of CMS, which is an inactive precursor. In the body, CMS is metabolized into various metabolites including colistin or is discharged through urine. In contrast, active metabolite colistin is hardly discharged through urine, and is removed through non-renal elimination, but the accurate extracorporeal elimination mechanism is still unknown. CMS reaches the peak serum concentration in 10 minutes from intravenous administration, and its half-life is 2.2 hours while the half-life of colistin 18.5 hours.
With regard to the bactericidal activity of colistin, the unbound area under the concentration-time curve/minimum inhibitory concentration (fAUC/MIC) is important, and adequate exposure to the drug has been known to be important for curative effect, but it is still controversial what the optimal dose and interval are. Although the drug has been used long, the accurate measuring of colistin blood concentration became possible only in the mid 2000s and, therefore, pharmacokinetic research on the drug has been conducted relatively recently and there is increasing interest in the validity of established uses, adequate uses, therapeutic drug monitoring, etc. Two of the established uses of the drug are intravenous administration of 2.5~5mg/kg/day divided into 2~4 times to patients with normal renal function, adjusting the dose and interval of administration according to renal function (package insert), and the administration of loading dose followed by 2~3 times of administration depending on renal function. The major side effects of colistin are nephrotoxicity and neurotoxicity, and according to a recent study, the incidence of nephrotoxicity caused by colistin was 30~60%. Renal insufficiency is more frequent when vancomycin is used together in VAP. Renal insufficiency is known to be reversible, but some cases require dialysis. Known risk factors of renal insufficiency include cumulative CMS dose, combined use of drugs inducing renal insufficiency, female, and age.
There have been ex vivo studies for assessing the bactericidal effect of colistin for exploring its adequate uses and case studies for evaluating the risk factors of nephrotoxicity, one of the major side effects yet there are still controversial issues related to the drug. Furthermore, as most of these studies were conducted with Western subjects, their results are hardly applicable to Koreans as they are. Thus, this study purposed to examine the adequate range of therapeutic concentration for Korean people.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Kyonggido
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Goyang, Kyonggido, Korea, Republic of, 411-773
- DongGuk University ilsan Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- All adult patients (aged ≥18 years)
- Microbiological evidence (sputum, urine, blood) of infection due to carbapenem-resistant Acinetobacter baumannii during hospitalization
- Intravenous Colistimethate sodium treated patient with Acinetobacter baumannii infection who fulfill the above criteria
- Patients who agree to the gathering clinical information by means of an informed consent
Exclusion Criteria:
- Pregnancy and lactating women
- Patients receiving Colistimethate sodium therapy for <48 hours
- Patient of chronic renal disease defined as a Creatinine clearance <10 mL/min, Or requirement for peritoneal or hemo-dialysis or hemofiltration
- Known hypersensitivity to Colistimethate sodium
- Receiving intravenous colistin therapy within the past 30 days
- Patients treated with nebulized Colistimethate sodium
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in plasma drug concentration between patients with nephrotoxicity and those without
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. Nephrothoxicity was determined during colistin use.
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- Criteria for diagnosing nephrotoxicity: Creatinine clearance (CrCL) decreases to 50% of the baseline value or serum creatinine concentration (SCr) doubles, or renal replacement therapy is required.
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Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. Nephrothoxicity was determined during colistin use.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in plasma drug concentration between patients showing clinical cure or improvement and those of treatment failure
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. Clinical outcome was determined at the final day of colistin use.
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Criteria for clinical cure/improvement:
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Participants will be followed for the duration of hospital stay, an expected average of 2-3wks. Clinical outcome was determined at the final day of colistin use.
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Difference in plasma drug concentration according to microbiological response
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks.
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- Microbiological response: Pathogens are not cultured at the end of treatment.
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Participants will be followed for the duration of hospital stay, an expected average of 2-3wks.
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Difference in plasma drug concentration according to in-hospital mortality
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-5wks.
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Participants will be followed for the duration of hospital stay, an expected average of 2-5wks.
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Difference in plasma drug concentration according to the RIFLE Criteria for nephrotoxicity
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks.
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Participants will be followed for the duration of hospital stay, an expected average of 2-3wks.
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Risk factors associated with nephrotoxicity
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3wks.
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Use of NSAIDS or other antibiotics, age and sex etc. associated with nephrotoxicity will be analyzed.
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Participants will be followed for the duration of hospital stay, an expected average of 2-3wks.
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Difference in plasma drug concentration between patients with abnormality of liver function.
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3ks.
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Participants will be followed for the duration of hospital stay, an expected average of 2-3ks.
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Difference in plasma drug concentration between patients with abnormality of thrombocytopenia.
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3ks.
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Participants will be followed for the duration of hospital stay, an expected average of 2-3ks.
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Difference in plasma drug concentration between patients with abnormality of neuropathy.
Time Frame: Participants will be followed for the duration of hospital stay, an expected average of 2-3ks.
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Participants will be followed for the duration of hospital stay, an expected average of 2-3ks.
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Young-Soon Yoon, professor, DongGuk University
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2014-128
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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