CONAN: Concentration of Antimicrobials in Catheter-lock Solutions

Sponsor

Clinica Universidad de Navarra, Universidad de Navarra (Other)

Overall Status

Unknown status

CT.gov ID

NCT01592032

Collaborator

University of Navarrra Hospital (Clinica Universitaria) (Other)

125

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Catheter-Related Infections Bacteremia.	Drug: Vancomycin antimicrobial-lock solution Drug: Teicoplanin antimicrobial-lock solution Drug: Linezolid antimicrobial-lock solution Drug: Daptomycin antimicrobial-lock solution Drug: Tigecycline antimicrobial-lock solution	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

125 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Concentration and Antibiotic Activity in Antibiotic Lock Solutions

Study Start Date :

May 1, 2012

Actual Primary Completion Date :

Jan 1, 2015

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
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.	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.
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.	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.
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.	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.
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.	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.
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.	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.

Outcome Measures

Primary Outcome Measures

Antimicrobial concentration of catheter-lock solutions at the end of port indwelling time. [1 to 10 days]

Secondary Outcome Measures

Bioactivity of antimicrobials in lock solutions at the end of port indwelling time. [1 to 10 days]
Anticoagulant activity of antimicrobial-lock solutions at the end of port indwelling time. [1 to 10 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinica Universidad de Navarra	Pamplona	Navarra	Spain	31008

Sponsors and Collaborators

Clinica Universidad de Navarra, Universidad de Navarra
University of Navarrra Hospital (Clinica Universitaria)

Investigators

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