Safety and Efficacy Study of Inhaled AmBisome for Prevention of Aspergillus Colonization in Lung Transplant Recipients

October 18, 2011 updated by: University Health Network, Toronto

A Pilot Study to Determine the Safety and Clinical Efficacy of Once-Weekly Inhaled AmBisome for the Prevention of Aspergillus Colonization in Lung Transplant Recipients

Lung transplant recipients have the highest rate of Invasive Aspergillus (IA)infection among solid organ transplant recipients. The most important risk factor for the development of IA (which is associated with disease and death) is colonization of the organism in the respiratory tract.

Azoles are used to prevent the development of IA. Puffers containing antifungal medication can be used to treat the lungs without the need to worry about the medication interactions & side-effects in the blood. An example of this is the aerosolized amphotericin B. Its use is limited by the patients' tolerating this medication that may cause cough, nausea & contraction of the air pathways.

The lipid preparation is better tolerated and has longer dosing interval than inhaled amphotericin B. The investigators propose a pilot study to determine the long-term safety of inhaled AmBisome administration of drug and generate the preliminary data on the effectiveness of this drug to prevent aspergillus colonization.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

In this pilot study, our main aims are:

  1. To determine the safety of once weekly Inhaled AmBisome prophylaxis in preventing the development of Aspergillus colonization in lung transplant recipients at one year of prophylaxis.
  2. To generate the preliminary data on the efficacy of Inhaled AmBisome (Astellas) loading dose (1mg/kg/day for four days) initially followed by q weekly dosage to complete 1 year in lung transplant recipients as compared to no prophylaxis by assessing the rate of fungal colonization/infections between the groups.

Study Type

Interventional

Enrollment (Anticipated)

4

Phase

  • Phase 2

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

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
        • University Health Network/ Toronto General Hospital

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Single or double lung transplant recipients who are at least one year out of transplantation.
  2. Age >18yrs of age
  3. Able to understand and complete informed consent.

Exclusion Criteria:

  1. Pregnant woman or woman capable of bearing children, who will not perform urine pregnancy test.
  2. Nursing mothers.
  3. Subjects with hypersensitivity to Amphotericin deoxycholate or liposomal Amphotericin.
  4. Subjects with a past history of bronchospasm associated with aerosol drug use.
  5. Subjects with active bacterial or viral infection as defined by the current use of non-prophylactic antibiotic anti-viral medications.
  6. Subjects treated with cytolytic medications (Campath /Thymoglobulin) within the last month.
  7. Subjects with an FEV1< 30% Predicted or FVC% <30%.
  8. Subjects requiring supplemental oxygen.
  9. Receipt of Inhaled or IV Amphotericin B within last 30 days.
  10. Subjects with known fungal infection as per MSG Criteria on therapy with antifungal drugs or diagnosed on the day of bronchoscopy.
  11. Current use of azoles active against molds (Voriconazole, itraconazole, posaconazole) for the prophylaxis.
  12. Serum creatinine > 150 mmol/L on the day of clinic visit.
  13. Liver enzymes ALT/ AST/ Alkphos greater than two times upper limit of normal.
  14. Concurrent intravenous aminoglycoside use.
  15. Subjects with fever > 38.2°C.
  16. Subjects on mechanical ventilation.
  17. Expected survival less than 6 months.
  18. Re-transplants and heart/lung transplant patients.

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Control
Standard of care group. Medication as prescribed by the primary physician would be used by this group. Such medications might include azoles as voriconazole
Drug: Regular standard of care medication
Drug for this group is at the physician's discretion. Patients in this group receive the standard of care medication currently implemented at the Institution. Example would be voriconazole
Experimental: liposomal amphotericin B (AmBisome ®)
Inhaled Liposomal preparation of Amphotericin B.
Drug: Ambisome ®
liposomal amphotericin B

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pulmonary Function
Time Frame: Day 1 to 12 months
Assess pulmonary function measurements i.e. changes in FEV1 (Forced Expiratory Volume 1), changes in FVC (Forced Vital Capacity) while receiving inhaled liposomal amphotericn B.
Day 1 to 12 months
Symptoms
Time Frame: Day 1 to 12months
Assess onset of symptoms including headache, dizziness and fatigue, fever, nausea, vomiting, wheezing, cough, shortness of breath, and taste preservation, while receiving inhaled liposomal amphotericin B
Day 1 to 12months
Renal or Hepatic dysfunction and Neutropenia
Time Frame: Day 1 to 12 months
Assess the development of renal or hepatic dysfunction and neutropenia by measuring serum creatinine liver enzymes and white blood cells
Day 1 to 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of Invasive fungal infection
Time Frame: 1 year

Measure the time in months from randomization of study participants to diagnosis of invasive fungal infection (proven or probable). Measure the time in months from randomization to death for study participants.

Assessment of the quality of life at the baseline Month 0, 3, 6, 9 and 12 months based on responses to a questionnaire. These include responses to general questions to rate the level of emotions and the general well being of the study participants. These responses are rated as never, sometimes, often or always experienced.
1 year

Collaborators and Investigators

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

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Shahid Husain, M.D M.Sc, University Health Network, Toronto

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

January 1, 2012

Primary Completion (Anticipated)

January 1, 2014

Study Completion (Anticipated)

January 1, 2014

Study Registration Dates

First Submitted

November 22, 2010

First Submitted That Met QC Criteria

December 3, 2010

First Posted (Estimate)

December 6, 2010

Study Record Updates

Last Update Posted (Estimate)

October 19, 2011

Last Update Submitted That Met QC Criteria

October 18, 2011

Last Verified

October 1, 2011

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AGM201000428

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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