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Concentration of Antimicrobials in Catheter-lock Solutions (CONAN)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of Navarrra Hospital (Clinica Universitaria)
Information provided by (Responsible Party):
José Luis del Pozo, Clinica Universidad de Navarra, Universidad de Navarra
ClinicalTrials.gov Identifier:
NCT01592032
First received: April 24, 2012
Last updated: February 18, 2015
Last verified: February 2015

April 24, 2012
February 18, 2015
May 2012
January 2015   (final data collection date for primary outcome measure)
Antimicrobial concentration of catheter-lock solutions at the end of port indwelling time. [ Time Frame: 1 to 10 days ] [ Designated as safety issue: No ]
  • Antibiotic concentration in catheter-lock solutions at the end of day 1. [ Time Frame: 1 day ] [ Designated as safety issue: Yes ]
    25 patients will be randomized in groups of 5 patients. The groups are vancomycin, teicoplanin, linezolid, daptomycin and tigecycline. At the end of day 1 the concentration of vancomycin, teicoplanin and daptomycin will be performed by HPLC. The concentration of linezolid and tigecycline will be assessed by LC-MS. The cutt-off value for antibiotic media concentration in each randomized group is 1mg/ml. A confirmed antibiotic concentration media value >1mg/ml will allow continuing with next 25 patients to be randomized for 3 days of catheter lock. Any of the arms will be interrupted if <1mg/ml.
  • Antibiotic concentration in catheter-lock solutions at the end of day 3. [ Time Frame: 3 days ] [ Designated as safety issue: Yes ]
    The arms that achieved >1mg/ml of antibiotic media concentration will continue with the catheter-lock (CL). Another 25 patients will be randomized for the same antibiotic lock solutions for 3 days. At the end of day 3 of CL, the concentration of vancomycin, teicoplanin and daptomycin will be performed by HPLC. The concentration of linezolid and tigecycline will be assessed by LC-MS. Again, a confirmed antibiotic concentration media value >1mg/ml will allow continuing with another 25 patients to be randomized for the 5 days catheter lock solution. Any of the arms will be interrupted if <1mg/ml.
  • Antibiotic concentration in catheter-lock solutions at the end of day 5. [ Time Frame: 5 days ] [ Designated as safety issue: Yes ]
    The arms that reached >1mg/ml of antibiotic media concentration in the 3 days groups will continue with a new group of 25 patients that will be randomized for the same antibiotic lock solutions for 5 days. At the end of day 5, the concentration of vancomycin, teicoplanin and daptomycin will be performed by HPLC. The concentration of linezolid and tigecycline will be assessed by LC-MS. Again, a confirmed antibiotic concentration media value >1mg/ml will allow continuing with new 25 patients to be randomized for the 7 days catheter lock solution. Any of the arms will be interrupted if <1mg/ml.
  • Antibiotic concentration in catheter-lock solutions at the end of day 7. [ Time Frame: 7 days ] [ Designated as safety issue: Yes ]
    The arms with >1mg/ml of antibiotic media concentration in the 5 days groups will continue with another 25 patients that will be randomized for the same antibiotic lock solutions for 10 days. At the end of day 7, the concentration of vancomycin, teicoplanin and daptomycin will be performed by HPLC. The concentration of linezolid and tigecycline will be assessed by LC-MS. Again, a confirmed antibiotic concentration media value >1mg/ml will allow continuing with a new group of 25 patients to be randomized for the 10 days of catheter lock solution. Any of the arms will be interrupted if <1mg/ml.
  • Antibiotic concentration in catheter-lock solutions at the end of day 10. [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
    The arms with > 1mg/ml of antibiotic media concentration in the 7 days groups of catheter lock will continue with the last 25 patients that will be randomized for the same antibiotic lock solutions for 10 days. As in the previous groups, at the end of day 10, the concentration of vancomycin, teicoplanin and daptomycin will be performed by HPLC. The concentration of linezolid and tigecycline will be assessed by LC-MS. All data obtained will be registered. At this point the study will be finished.
Complete list of historical versions of study NCT01592032 on ClinicalTrials.gov Archive Site
  • Bioactivity of antimicrobials in lock solutions at the end of port indwelling time. [ Time Frame: 1 to 10 days ] [ Designated as safety issue: No ]
  • Anticoagulant activity of antimicrobial-lock solutions at the end of port indwelling time. [ Time Frame: 1 to 10 days ] [ Designated as safety issue: No ]
  • Antimicrobial activity of antibiotics in lock solutions at the end of lock time assigned. [ Time Frame: 1, 3, 5, 7, and 10 days ] [ Designated as safety issue: Yes ]
    Antibiotic antimicrobial activity will be assessed by a biological assay using an ATCC strain of Micrococcus spp. The results will show values of MIC, MBC and time-kill curves.
  • Anticoagulant activity of heparin in antibiotic lock solutions at the end of lock time assigned. [ Time Frame: 1, 3, 5, 7 and 10 days ] [ Designated as safety issue: Yes ]
    Anticoagulant activity of heparin will be assessed by activated partial thromboplastin time. APPT values are given in seconds.
Not Provided
Not Provided
 
Concentration of Antimicrobials in Catheter-lock Solutions
Concentration and Antibiotic Activity in Antibiotic Lock Solutions

The antibiotic lock technique (ALT) is used as local treatment for Catheter-Related Bacteremia (CRB). It consists in the administration of a concentrated antimicrobial solution with a calculated volume to fill the lumen of the catheter. The lock solution is indwelled within the catheter for a defined period of hours or days before been removed.

Currently, the Infectious Diseases Society of America (IDSA) Guidelines for treatment and management of CRB, recommends to change the antibiotic solution every 24 hours.

The investigators expect to determine the stability of the concentration of vancomycin, teicoplanin, linezolid, daptomycin and tigecycline used in lock solutions, and thus to assay the optimal timeframe that the concentration of antibiotic used in lock solution keeps its in vivo antimicrobial activity.

Study Hypothesis: An antibiotic lock solution maintains in vivo concentration and antimicrobial activity for at least 10 days after its infusion inside a subcutaneous port catheter.

Primary Objective: Assess the antimicrobial concentration of catheter-lock solutions at the end of port indwelling time. Secondary Objectives: 1) Assess bioactivity of antimicrobials in lock solutions at the end of port indwelling time. 2) Assess anticoagulant activity of antimicrobial-lock solutions at the end of port indwelling time.

Methods: Randomized, open, block allocation according to time of indwelling of the antimicrobial-lock within the ports, unicentric, clinical trial in patients older than 18 years old with a venous port implanted at Clínica Universidad de Navarra. Intevention: Randomization of 5 patients into one of five antimicrobial-lock solution arms for 1, 3, 5, 7 and 10 days according to HPLC corrected by urea gradient. Any study arm can be stopped at any time from day 1 to day 10, in case of antimicrobial concentration would be less than 1 mg/mL.

At the end of each antimicrobial lock time frame of ports (1, 3, 5, 7 and 10 days), the antimicrobial concentration will be determined by high performance liquid chromatography (HPLC) and corrected by urea gradient. The cut-off for the median antimicrobial concentration is 1 mg/mL.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Catheter-Related Infections
  • Bacteremia.
  • Drug: Vancomycin antimicrobial-lock solution
    Randomization of 5 patients into vancomycin antimicrobial-lock solution arm for 1, 3, 5, 7 and 10 days according to HPLC corrected by urea gradient. The arm can be stopped any time from day 1 to day 10 in case of antimicrobial concentration less than 1 mg/mL.
    Other Names:
    • vancomycin: vancomicina sala 500 mg vial.
    • sodium heparin 1%, 5000 IU/5ml.
    • sodium chloride 0,9% 10 ml vial.
  • Drug: Teicoplanin antimicrobial-lock solution
    Randomization of 5 patients into teicoplanin antimicrobial-lock solution arm for 1, 3, 5, 7 and 10 days according to HPLC corrected by urea gradient. The arm can be stopped any time from day 1 to day 10 in case of antimicrobial concentration less than 1 mg/mL.
    Other Names:
    • teicoplanin: targocid 200 mg vial.
    • sodium heparin 1%, 5000 IU/5ml.
    • sodium chloride 0,9% 10 ml vial.
  • Drug: Linezolid antimicrobial-lock solution
    Randomization of 5 patients into linezolid antimicrobial-lock solution arm for 1, 3, 5, 7 and 10 days according to HPLC corrected by urea gradient. The arm can be stopped any time from day 1 to day 10 in case of antimicrobial concentration less than 1 mg/mL.
    Other Names:
    • linezolid: zyloxid 2 mg/ml, 300 ml vial.
    • sodium heparin 1%, 5000 IU/5ml.
    • sodium chloride 0,9% 10 ml vial.
  • Drug: Daptomycin antimicrobial-lock solution
    Randomization of 5 patients into daptomycin antimicrobial-lock solution arm for 1, 3, 5, 7 and 10 days according to HPLC corrected by urea gradient. The arm can be stopped any time from day 1 to day 10 in case of antimicrobial concentration less than 1 mg/mL.
    Other Names:
    • daptomycin: cubicin 350 mg vial.
    • sodium heparin 1%, 5000 IU/5ml.
    • lactated ringer´s solution 500 ml viaflo.
  • Drug: Tigecycline antimicrobial-lock solution
    Randomization of 5 patients into tigecycline antimicrobial-lock solution arm for 1, 3, 5, 7 and 10 days according to HPLC corrected by urea gradient. The arm can be stopped any time from day 1 to day 10 in case of antimicrobial concentration less than 1 mg/mL.
    Other Names:
    • tigecycline: tygacil 50 mg vial.
    • sodium chloride 0,9% 10 ml vial.
    • sodium heparin 1%, 5000 IU/5ml.
  • Experimental: Vancomycin antimicrobial-lock
    Vancomycin antimicrobial-lock solution. Dosage: 2 mg/mL. Dosage form: liquid in syringe. Frequency: 1. Duration: from 1 to 10 days according to HPLC corrected by urea gradient.
    Intervention: Drug: Vancomycin antimicrobial-lock solution
  • Experimental: Teicoplanin antimicrobial-lock
    Teicoplanin antimicrobial-lock solution. Dosage: 10 mg/mL. Dosage form: liquid in syringe. Frequency: 1. Duration: from 1 to 10 days according to HPLC corrected by urea gradient.
    Intervention: Drug: Teicoplanin antimicrobial-lock solution
  • Experimental: Linezolid antimicrobial-lock
    Linezolid antimicrobial-lock solution. Dosage: 1.8 mg/mL. Dosage form: liquid in syringe. Frequency: 1. Duration: from 1 to 10 days according to HPLC corrected by urea gradient.
    Intervention: Drug: Linezolid antimicrobial-lock solution
  • Experimental: Daptomycin antimicrobial-lock
    Daptomycin antimicrobial-lock solution. Dosage: 5 mg/mL. Dosage form: liquid in syringe. Frequency: 1. Duration: from 1 to 10 days according to HPLC corrected by urea gradient.
    Intervention: Drug: Daptomycin antimicrobial-lock solution
  • Experimental: Tigecycline antimicrobial-lock
    Tigecycline antimicrobial-lock solution. Dosage: 4.5 mg/mL. Dosage form: liquid in syringe. Frequency: 1. Duration: from 1 to 10 days according to HPLC corrected by urea gradient.
    Intervention: Drug: Tigecycline antimicrobial-lock solution

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
125
December 2015
January 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Intravenous access port recently inserted (≤ 3 days of insertion).
  • Intravenous access port inserted more than 3 days before informed consent form signing patient. In this case, a blood sample from the catheter will be drawn for blood culture before administration of the antibiotic lock solution.
  • Informed Consent Form Signed.

Exclusion Criteria:

  • Patients with confirmed or suspected local or systemic infection related to the catheter.
  • Reported allergy or intolerance to the antibiotic employed for study lock solutions.
  • Patients receiving oral, intravenous or intramuscular antibiotic treatment at the moment of inclusion in the clinical trial.
  • Patients receiving oral, intravenous or subcutaneous anticoagulant treatment, in a higher dose than the one used for venous thrombosis prophylaxis at the moment of inclusion in the clinical trial.
  • Patients younger than 18 years old.
  • Pregnant women or women in nursing period.
  • Personal incapacity to subscribe the informed consent to participate in the clinical trial.

Patient Replacement Criteria:

All patients and/or their legal representatives will be inform that they can leave the clinical trial in whenever they wish to do it, without prejudice to their medical attention.

Also, according to the criteria of the principal investigator, a patient could be separated from the clinical trial. The reasons to separate a patient from the study and replace him/her are:

  • Severe adverse reaction that could threat the life of the patient.
  • Resolution of the patient or from his/her legal representative to abandon the study.
  • No attend to the extraction visit date.
  • Development of clinical inconveniences that may indicate to abandon the study in behalf of the patient.
  • While antibiotic lock solution is within the port, manipulation or use of the port for administration of any kind of medication or fluid.
  • Impossibility to extract 4 ml of the antibiotic lock solution from the port.
  • Impossibility to extract 5 ml of peripheral blood sample at the moment of extraction of the antibiotic lock solution.
  • Use of any of the prohibited medications during the antibiotic lock solution is inside the port.
  • Intentionally wish of the patient in abandoning the study before or after antibiotic lock solution has been administered, or while the antibiotic lock solution is inside the port.

All patients who abandon the study or would be separated from the study for the exposed reasons, will be replaced for new candidates who fulfil the inclusion criteria and have signed the informed consent form.

Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Spain
 
NCT01592032
CAS110775, 2010-023814-29
Yes
Not Provided
Not Provided
José Luis del Pozo, Clinica Universidad de Navarra, Universidad de Navarra
Clinica Universidad de Navarra, Universidad de Navarra
University of Navarrra Hospital (Clinica Universitaria)
Principal Investigator: JOSE L DEL POZO, MD. Ph. D. Clinica Universidad de Navarra
Study Chair: CESAR E BUSTOS, MD. Clinica Universidad de Navarra
Study Chair: AITZIBER AGUINAGA, Pharm. D. Clinica Universidad de Navarra
Study Chair: JOSE R YUSTE, MD. Ph.D. Clinica Universidad de Navarra
Study Chair: JOSE R AZANZA, MD. Ph.D. Clinica Universidad de Navarra
Clinica Universidad de Navarra, Universidad de Navarra
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP