Concentration of Antimicrobials in Catheter-lock Solutions

NCT01592032 | Unknown Phase 4 DMC

• 2 other identifiers: CAS1107752010-023814-29
• Study Type: interventional
• Target: 125
• Locations: 1 country
• Sites: 1

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.

Conditions

Catheter-Related Infections; Bacteremia.

Keywords

Antibiotic-lock technique.; In vivo antimicrobial concentration.; Antimicrobial bioactivity.

Outcome Measures

Primary Outcomes (1)

• Antimicrobial concentration of catheter-lock solutions at the end of port indwelling time.

  1 to 10 days

Secondary Outcomes (2)

• 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

Study Arms (5)

Vancomycin antimicrobial-lock

EXPERIMENTAL

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

Teicoplanin antimicrobial-lock

EXPERIMENTAL

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

Linezolid antimicrobial-lock

EXPERIMENTAL

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

Daptomycin antimicrobial-lock

EXPERIMENTAL

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

Tigecycline antimicrobial-lock

EXPERIMENTAL

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

Interventions

Vancomycin antimicrobial-lock solution DRUG

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.

Also known as: vancomycin: vancomicina sala 500 mg vial., sodium heparin 1%, 5000 IU/5ml., sodium chloride 0,9% 10 ml vial.

Vancomycin antimicrobial-lock

Teicoplanin antimicrobial-lock solution DRUG

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.

Also known as: teicoplanin: targocid 200 mg vial., sodium heparin 1%, 5000 IU/5ml., sodium chloride 0,9% 10 ml vial.

Teicoplanin antimicrobial-lock

Linezolid antimicrobial-lock solution DRUG

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.

Also known as: linezolid: zyloxid 2 mg/ml, 300 ml vial., sodium heparin 1%, 5000 IU/5ml., sodium chloride 0,9% 10 ml vial.

Linezolid antimicrobial-lock

Daptomycin antimicrobial-lock solution DRUG

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.

Also known as: daptomycin: cubicin 350 mg vial., sodium heparin 1%, 5000 IU/5ml., lactated ringer´s solution 500 ml viaflo.

Daptomycin antimicrobial-lock

Tigecycline antimicrobial-lock solution DRUG

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.

Also known as: tigecycline: tygacil 50 mg vial., sodium chloride 0,9% 10 ml vial., sodium heparin 1%, 5000 IU/5ml.

Tigecycline antimicrobial-lock

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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 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.

Sponsors & Collaborators

• Clinica Universidad de Navarra, Universidad de Navarra: lead
• University of Navarrra Hospital (Clinica Universitaria): collaborator

Study Sites (1)

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Related Publications (12)

• 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.

  PMID: 22340450 RESULT

• 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.

  PMID: 19713086 RESULT

• del Pozo JL. Role of antibiotic lock therapy for the treatment of catheter-related bloodstream infections. Int J Artif Organs. 2009 Sep;32(9):678-88. doi: 10.1177/039139880903200918.

  PMID: 19882553 RESULT

• Mermel LA, Allon M, Bouza E, Craven DE, Flynn P, O'Grady NP, Raad II, Rijnders BJ, Sherertz RJ, Warren DK. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2009 Jul 1;49(1):1-45. doi: 10.1086/599376.

  PMID: 19489710 RESULT

• del Pozo JL, Patel R. The challenge of treating biofilm-associated bacterial infections. Clin Pharmacol Ther. 2007 Aug;82(2):204-9. doi: 10.1038/sj.clpt.6100247. Epub 2007 May 30.

  PMID: 17538551 RESULT

• 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.

  PMID: 16641463 RESULT

• 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.

  PMID: 18349379 RESULT

• 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.

  PMID: 17403700 RESULT

• 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.

  PMID: 19026506 RESULT

• 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.

  PMID: 17353249 RESULT

• 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.

  PMID: 16155063 RESULT

• 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.

  PMID: 14638511 RESULT

MeSH Terms

Conditions

Catheter-Related Infections; Bacteremia

Interventions

Heparin

Condition Hierarchy (Ancestors)

Infections; Bacterial Infections; Bacterial Infections and Mycoses; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• JOSE L DEL POZO, MD. Ph. D.

  Clinica Universidad de Navarra

  PRINCIPAL INVESTIGATOR

• 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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor, Ph. D.

Study Record Dates

• First Submitted: April 24, 2012
• First Posted: May 4, 2012
• Study Start: May 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 19, 2015

Record last verified: 2015-02

Locations

ES (1)