Clinical trial NCT01592032: Concentration of Antimicrobials in Catheter-lock Solutions
Official title: Concentration and Antibiotic Activity in Antibiotic Lock Solutions
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Catheter-Related Infections
Bacteremia.
Keywords: Antibiotic-lock technique.
In vivo antimicrobial concentration.
Antimicrobial bioactivity.
Lead sponsor: Clinica Universidad de Navarra, Universidad de Navarra
Sponsor class: OTHER
Collaborators: name: University of Navarrra Hospital (Clinica Universitaria)
First posted: 2012-05-04
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Antimicrobial concentration of catheter-lock solutions at the end of port indwelling time.
timeFrame: 1 to 10 days
Secondary outcomes:
measure: Bioactivity of antimicrobials in lock solutions at the end of port indwelling time.
timeFrame: 1 to 10 days
measure: Anticoagulant activity of antimicrobial-lock solutions at the end of port indwelling time.
timeFrame: 1 to 10 days
Other outcomes:
Locations:
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
Study officials:
affiliation: Clinica Universidad de Navarra
name: JOSE L DEL POZO, MD. Ph. D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Clinica Universidad de Navarra
name: CESAR E BUSTOS, MD.
role: STUDY_CHAIR
affiliation: Clinica Universidad de Navarra
name: AITZIBER AGUINAGA, Pharm. D.
role: STUDY_CHAIR
affiliation: Clinica Universidad de Navarra
name: JOSE R YUSTE, MD. Ph.D.
role: STUDY_CHAIR
affiliation: Clinica Universidad de Navarra
name: JOSE R AZANZA, MD. Ph.D.
role: STUDY_CHAIR
References:
citation: Del Pozo JL, Rodil R, Aguinaga A, Yuste JR, Bustos C, Montero A, Espinosa G, Garcia-Fernandez N. Daptomycin lock therapy for grampositive long-term catheter-related bloodstream infections. Int J Clin Pract. 2012 Mar;66(3):305-8. doi: 10.1111/j.1742-1241.2011.02830.x.
citation: Del Pozo JL, Garcia Cenoz M, Hernaez S, Martinez A, Serrera A, Aguinaga A, Alonso M, Leiva J. Effectiveness of teicoplanin versus vancomycin lock therapy in the treatment of port-related coagulase-negative staphylococci bacteraemia: a prospective case-series analysis. Int J Antimicrob Agents. 2009 Nov;34(5):482-5. doi: 10.1016/j.ijantimicag.2009.06.020. Epub 2009 Aug 26.
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citation: Sherertz RJ, Boger MS, Collins CA, Mason L, Raad II. Comparative in vitro efficacies of various catheter lock solutions. Antimicrob Agents Chemother. 2006 May;50(5):1865-8. doi: 10.1128/AAC.50.5.1865-1868.2006.
citation: Fennell JP, O'Donohoe M, Cormican M, Lynch M. Linezolid lock prophylaxis of central venous catheter infection. J Med Microbiol. 2008 Apr;57(Pt 4):534-535. doi: 10.1099/jmm.0.47665-0.
citation: LaPlante KL, Mermel LA. In vitro activity of daptomycin and vancomycin lock solutions on staphylococcal biofilms in a central venous catheter model. Nephrol Dial Transplant. 2007 Aug;22(8):2239-46. doi: 10.1093/ndt/gfm141. Epub 2007 Apr 1.
citation: Del Pozo JL, Alonso M, Serrera A, Hernaez S, Aguinaga A, Leiva J. Effectiveness of the antibiotic lock therapy for the treatment of port-related enterococci, Gram-negative, or Gram-positive bacilli bloodstream infections. Diagn Microbiol Infect Dis. 2009 Feb;63(2):208-12. doi: 10.1016/j.diagmicrobio.2008.10.004. Epub 2008 Nov 21.
citation: Raad I, Hanna H, Jiang Y, Dvorak T, Reitzel R, Chaiban G, Sherertz R, Hachem R. Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm. Antimicrob Agents Chemother. 2007 May;51(5):1656-60. doi: 10.1128/AAC.00350-06. Epub 2007 Mar 12.
citation: Robinson JL, Tawfik G, Saxinger L, Stang L, Etches W, Lee B. Stability of heparin and physical compatibility of heparin/antibiotic solutions in concentrations appropriate for antibiotic lock therapy. J Antimicrob Chemother. 2005 Nov;56(5):951-3. doi: 10.1093/jac/dki311. Epub 2005 Sep 9.
citation: Labthavikul P, Petersen PJ, Bradford PA. In vitro activity of tigecycline against Staphylococcus epidermidis growing in an adherent-cell biofilm model. Antimicrob Agents Chemother. 2003 Dec;47(12):3967-9. doi: 10.1128/AAC.47.12.3967-3969.2003.