Clinical trial NCT01254708: Safety and Efficacy Study of Inhaled AmBisome for Prevention of Aspergillus Colonization in Lung Transplant Recipients
Official title: 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
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Lung Transplant Recipient
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2010-12-06
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pulmonary Function
timeFrame: Day 1 to 12 months
measure: Symptoms
timeFrame: Day 1 to 12months
measure: Renal or Hepatic dysfunction and Neutropenia
timeFrame: Day 1 to 12 months
Secondary outcomes:
measure: Presence of Invasive fungal infection
timeFrame: 1 year
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: University Health Network/ Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Shahid Husain, M.D M.Sc
role: PRINCIPAL_INVESTIGATOR
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