Antifungal Locks to Treat Fungal-Related Central Line Infections - Full Text View

Sponsor:	University of Pittsburgh
Collaborator:	Astellas Pharma Inc
Information provided by:	University of Pittsburgh
ClinicalTrials.gov Identifier:	NCT00936910

Purpose

The purpose of this study is to evaluate the usefulness of antifungal lock therapy with liposomal amphotericin B (Ambisome), in combination with systemic antifungal(s), in patients with catheter-related blood stream infections with fungal organisms, whose catheter has not been removed because of the continuing critical need for central line access. The primary group of potential patients will be those with intestinal insufficiency, including post-op small bowel transplant recipients.

The recommendation of the Infectious Disease Society of America is to remove all catheters with fungal infections and treat systemically for 14 days after the last positive culture. However, in certain intestinal failure patients, removal of an infected line might significantly reduce or eliminate intravenous (IV) access and create a life threatening situation. Thus, the investigators' aim is to determine the usefulness of antifungal lock therapy in intestinal failure patients whose catheter has not been removed. The investigators' hope is to salvage central line catheters rather than to remove them.

Condition	Intervention	Phase
Central Line Fungal Infections	Drug: amphotericin B liposomal (Ambisome)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	The Use of Antifungal Lock Therapy in Intestinal Failure and Other Patients

Resource links provided by NLM:

MedlinePlus related topics: Fungal Infections Molds

Drug Information available for: Amphotericin B

U.S. FDA Resources

Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:

The success of antifungal lock therapy (the primary endpoint) will be determined by whether or not the patient has at least 2 negative fungal cultures and the CVC was not removed. [ Time Frame: 5 days of antifungal lock treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

The number of days before the infected central line culture becomes negative [ Time Frame: 5 days of antifungal lock treatment ] [ Designated as safety issue: No ]
The development of fungal-related complications [ Time Frame: Usually 14-28 days ] [ Designated as safety issue: Yes ]
Test of cure catheter cultures on day 5 and day 30 post antifungal lock [ Time Frame: 45-55 days ] [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	September 2006
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	August 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Antifungal lock-treated patients: Experimental Intestinal failure and other patients with poor IV access and central line fungal-related infections	Drug: amphotericin B liposomal (Ambisome) After enrollment, antifungal therapy will be instituted consisting of both IV systemic and antifungal lock therapy. Systemic therapy will be Ambisome administered IV in a dose of 3-5 mg/kg/day (or other antifungal based upon standard of care) combined with antifungal lock therapy. The antifungal lock therapy consists of placing up to 2.3 ml of concentrated Ambisome (2 mg/ml) into the infected central venous catheter (CVC) and allowing it to dwell uninterruptedly for 8 to 12 hours per day for 10-14 days.

Arms

Assigned Interventions

Antifungal lock-treated patients: Experimental

Intestinal failure and other patients with poor IV access and central line fungal-related infections

Drug: amphotericin B liposomal (Ambisome)

After enrollment, antifungal therapy will be instituted consisting of both IV systemic and antifungal lock therapy. Systemic therapy will be Ambisome administered IV in a dose of 3-5 mg/kg/day (or other antifungal based upon standard of care) combined with antifungal lock therapy. The antifungal lock therapy consists of placing up to 2.3 ml of concentrated Ambisome (2 mg/ml) into the infected central venous catheter (CVC) and allowing it to dwell uninterruptedly for 8 to 12 hours per day for 10-14 days.

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Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Patients with intestinal insufficiency and central venous access.
Culture positive fungal-related CRBSI.
Females of childbearing potential will be eligible for the study.
Ambisome carries a category B Pregnancy Risk Factor. Since this is a minimal pregnancy risk category, no special precautions will be taken to determine that the patient is not pregnant.
HIV serostatus will not be determined for the purpose of participating in this study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00936910

Contacts

Contact: Bill McGhee, PharmD

412-692-5733

william.mcghee@chp.edu

Locations

United States, Pennsylvania
Children's Hospital of Pittsburgh	Recruiting
Pittsburgh, Pennsylvania, United States, 15201
Contact: Bill McGhee, PharmD 412-692-5733 william.mcghee@chp.edu
Sub-Investigator: Mike Green, MD
Sub-Investigator: Fuchs Julie, MD
Sub-Investigator: Martin Judy, MD
Sub-Investigator: Mazariegos George, MD
Sub-Investigator: Michaels Marian, MD
Sub-Investigator: Nowalk Andrew, MD
Sub-Investigator: Squires Robert, MD

Sponsors and Collaborators

University of Pittsburgh

Astellas Pharma Inc

Investigators

Principal Investigator:

Bill McGhee, PharmD

Children's Hospital of Pittsburgh of UPMC

More Information

Publications:

Hall K, Farr B. Diagnosis and management of long-term central venous catheter infections. J Vasc Interv Radiol. 2004 Apr;15(4):327-34. Review.

Mermel LA, Farr BM, Sherertz RJ, Raad II, O'Grady N, Harris JS, Craven DE; Infectious Diseases Society of America; American College of Critical Care Medicine; Society for Healthcare Epidemiology of America. Guidelines for the management of intravascular catheter-related infections. Clin Infect Dis. 2001 May 1;32(9):1249-72. Epub 2001 Apr 3. Review. No abstract available.

Raad I, Costerton W, Sabharwal U, Sacilowski M, Anaissie E, Bodey GP. Ultrastructural analysis of indwelling vascular catheters: a quantitative relationship between luminal colonization and duration of placement. J Infect Dis. 1993 Aug;168(2):400-7.

Schinabeck MK, Long LA, Hossain MA, Chandra J, Mukherjee PK, Mohamed S, Ghannoum MA. Rabbit model of Candida albicans biofilm infection: liposomal amphotericin B antifungal lock therapy. Antimicrob Agents Chemother. 2004 May;48(5):1727-32.

Johnson DC, Johnson FL, Goldman S. Preliminary results treating persistent central venous catheter infections with the antibiotic lock technique in pediatric patients. Pediatr Infect Dis J. 1994 Oct;13(10):930-1. No abstract available.

Viale P, Petrosillo N, Signorini L, Puoti M, Carosi G. Should lock therapy always be avoided for central venous catheter-associated fungal bloodstream infections? Clin Infect Dis. 2001 Dec 1;33(11):1947-8; author reply 1949-51. No abstract available.

Kuhn DM, George T, Chandra J, Mukherjee PK, Ghannoum MA. Antifungal susceptibility of Candida biofilms: unique efficacy of amphotericin B lipid formulations and echinocandins. Antimicrob Agents Chemother. 2002 Jun;46(6):1773-80.

Siegman-Igra Y, Anglim AM, Shapiro DE, Adal KA, Strain BA, Farr BM. Diagnosis of vascular catheter-related bloodstream infection: a meta-analysis. J Clin Microbiol. 1997 Apr;35(4):928-36.

Blot F, Nitenberg G, Chachaty E, Raynard B, Germann N, Antoun S, Laplanche A, Brun-Buisson C, Tancrède C. Diagnosis of catheter-related bacteraemia: a prospective comparison of the time to positivity of hub-blood versus peripheral-blood cultures. Lancet. 1999 Sep 25;354(9184):1071-7.

Wey SB, Mori M, Pfaller MA, Woolson RF, Wenzel RP. Hospital-acquired candidemia. The attributable mortality and excess length of stay. Arch Intern Med. 1988 Dec;148(12):2642-5.

Eppes SC, Troutman JL, Gutman LT. Outcome of treatment of candidemia in children whose central catheters were removed or retained. Pediatr Infect Dis J. 1989 Feb;8(2):99-104.

Dato VM, Dajani AS. Candidemia in children with central venous catheters: role of catheter removal and amphotericin B therapy. Pediatr Infect Dis J. 1990 May;9(5):309-14.

Nucci M, Anaissie E. Should vascular catheters be removed from all patients with candidemia? An evidence-based review. Clin Infect Dis. 2002 Mar 1;34(5):591-9. Epub 2002 Jan 24.

Castagnola E, Marazzi MG, Tacchella A, Giacchino R. Broviac catheter-related candidemia. Pediatr Infect Dis J. 2005 Aug;24(8):747. No abstract available.

Responsible Party:	Children's Hospital of Pittsburgh ( Bill McGhee, PharmD/Clinical Pharmacy Specialist )
Study ID Numbers:	Ambisome Locks at CHP
Study First Received:	July 2, 2009
Last Updated:	July 8, 2009
ClinicalTrials.gov Identifier:	NCT00936910 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Pittsburgh:

central line fungal infections
antifungal lock therapy
Ambisome lock therapy

Additional relevant MeSH terms:

Abelcet
Communicable Diseases
Amphotericin B
Anti-Infective Agents
Antiprotozoal Agents
Infection
Liposomal amphotericin B
Pharmacologic Actions

Anti-Bacterial Agents
Mycoses
Antiparasitic Agents
Antifungal Agents
Therapeutic Uses
Antibiotics, Antifungal
Amebicides

ClinicalTrials.gov processed this record on February 08, 2010