Antifungal Locks to Treat Fungal-related Central Line Infections

September 10, 2017 updated by: Bill McGhee

The Use of Antifungal Lock Therapy in Intestinal Failure and Other Patients

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 (IDSA) 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a descriptive study in intestinal failure patients with catheter-related blood stream infections (CRBSI) with fungal organisms. At present, the recommendation of the Infectious Disease Society of America (IDSA) is to remove all catheters with fungal infections and treat systemically for 14 days after the last positive culture (2). However, in intestinal failure patients who have limited IV access, removal of a line infected with Candida albicans, although recommended, might significantly reduce intravenous access and create a life threatening situation. Thus, the purpose of this study is to evaluate the use of antifungal lock therapy with liposomal amphotericin B (Ambisome) in combination with systemic antifungal therapy in patients with fungal CRBSI, whose catheter has not been removed because of the continuing critical need for central line access. The research methods are as follows:

  1. Study patients will consist of in-patients hospitalized at Children's Hospital of Pittsburgh. From our intestinal failure patients followed by GI, Transplant, and Pediatric Surgical Services, we plan to enroll 25 patients. In addition, other patients with similar concerns regarding limited central venous access with catheter-related candidal bloodstream infection may also be considered for this protocol.
  2. The primary group of potential patients in the study will be patients with intestinal insufficiency, including post-op small bowel recipients, whose intravenous access is limited. Thus, when a fungal CRBSI is suspected, retention of the CVC will be highly desirable. Additional subjects potentially eligible for this study would include children with cancer, those status-post bone marrow transplant, etc. who have limited central venous access and have a documented catheter-related bloodstream infection secondary to candida.
  3. Once the fungal infection is established, the patient will be approached to participate in the study. The investigator(s) will fully explain the study and its benefits and risks to the patient and/or parent or guardian (if legally appointed for research) and consent and assent will be obtained.

  4. Upon enrollment, antifungal therapy will be instituted consisting of both systemic and antifungal lock therapy.

    A. Ambisome at a dose of 3-5 mg/kg/day (or other appropriate antifungal based upon standard of care) will be administered intravenously B. Antifungal lock therapy with Ambisome will be administered. It consists of the placing up to 2.3 ml (based upon specific catheter types and volumes) of concentrated Ambisome into the infected CVC and allowing it to dwell uninterruptedly for 8 to 12 hours per day. The concentration of Ambisome is 2 mg/ml in sterile water (4).

  5. Patients enrolled in the study will receive routine clinical care as in-patients of CHP and be monitored appropriately from an infectious disease perspective including daily blood cultures. Patients will be examined clinically for evidence of fungal-related complications (e.g., septic arthritis, endocarditis, etc.).
  6. The duration of antifungal lock therapy (in addition to IV systemic antifungal therapy) will be 10-14 days.
  7. After 5 days of antifungal lock therapy, the patient with a persistently positive fungal blood culture will be deemed a failure and antifungal lock therapy will be discontinued. There will be no further antifungal lock therapy permissible via this protocol and data collection for the patient will be completed as soon as possible. The primary service will be responsible for the removal of the line.

  8. With successful lock therapy, additional blood cultures through the catheter will be obtained on day 5 and day 30 (or later if subject is still on systemic antifungal agents) post antifungal lock for a test of cure.

    • If a patient has a recurrence of fungal infection on culture on day 5 or day 30 post antifungal lock, pulse field gel electrophoresis will be performed on both the original and new isolate to determine if the fungal organism is the same.
    • If the organism is the same based upon electrophoretic analysis, treatment will be deemed a failure
    • If the organism is not the same, then another source for the infection will be investigated.
  9. Since the standard of care would have been to remove the CVC, the primary end point of the study will be the number and percent of patients who successfully received antifungal lock therapy, i.e., those patients with at least 2 negative fungal cultures before the completion of 5 days of antifungal lock therapy and whose CVCs were not removed. Secondary endpoints will include the number of days before the cultures become negative; the development of fungal-related complications (e.g., septic arthritis, endocarditis, etc.); and the development of recurrent candidemia on day 5 and day 30 post antifungal lock therapy.
  10. When medically appropriate, subjects may be discharged to complete their Ambisome® lock therapy at home. Instructions/training on how to administer lock therapy will be provided to the parents, guardian, or subject and contact with the research coordinator will be maintained while the patient is at home.
  11. A patient registry will be established and offered to all subjects with central line fungal infections treated with Ambisome® locks.

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • Children's Hospital of Pittsburgh

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 month to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Exclusion Criteria:

  • Patients less than 30 days of age
  • Patients greater than 21 years of age

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Antifungal lock-treated patients
Intestinal failure and other patients with poor IV access and central line fungal-related infections will receive intravenous systemic antifungal therapy plus the instillation of Ambisome locks into the infected catheter.
Drug: amphotericin B liposomal (Ambisome)
After enrollment, antifungal therapy will be instituted consisting of both systemic and antifungal lock therapy. Systemic therapy will be amphotericin B liposomal (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 sufficient amphotericin B liposomal (Ambisome [2 mg/ml]) lock solution into the infected central venous catheter (CVC) and allowing it to dwell uninterruptedly for 8 to 12 hours per day for 10-14 days (largest CVC = 2.3 mL).
Other Names:
  • Ambisome

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Patients With 2 Negative Fungal Cultures After 5 Days of Combined Systemic Antifungal and Antifungal Lock Therapy and the CVC Was Not Removed
Time Frame: 5 days of antifungal lock treatment
Records the number of patients with 2 negative fungal cultures after 5 days of combined systemic antifungal and antifungal lock therapy and the CVC was not removed
5 days of antifungal lock treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Number of Days Before the Infected Central Line Culture Becomes Negative
Time Frame: 5 days of antifungal lock treatment
Records the mean number of days required for the cultures to become negative
5 days of antifungal lock treatment
The Development of Fungal-related Complications
Time Frame: Usually 1-28 days
Records the number of fungal related adverse complications that occurred
Usually 1-28 days
Number of Participants With Negative Cultures on Day 5 and Day 30 During the Test of Cure Period Post Antifungal Lock
Time Frame: 30 days
Records the number of participants with 2 negative cultures who completed the trial and had (-) test of cure cultures on day 5 and 30
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bill McGhee

Collaborators

Astellas Pharma Inc

Investigators

  • Principal Investigator: Bill McGhee, PharmD, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2006

Primary Completion (Actual)

August 1, 2010

Study Completion (Actual)

September 1, 2010

Study Registration Dates

First Submitted

July 2, 2009

First Submitted That Met QC Criteria

July 8, 2009

First Posted (Estimate)

July 10, 2009

Study Record Updates

Last Update Posted (Actual)

October 10, 2017

Last Update Submitted That Met QC Criteria

September 10, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Ambisome Locks at CHP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

The entire data for all patients from the clinical trial has been published. The reference is: McGhee W, Michaels M, Martin, J, et al. Antifungal Lock Therapy with Liposomal Amphotericin B: A Prospective Trial. Journal of the Pediatric Infectious Diseases Society. 2016;5 (1): 80-4.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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