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

University Health Network, Toronto

Status and phase: Suspended; Phase 2

Conditions: Lung Transplant Recipient

Treatments: Drug: Ambisome ®; Drug: Regular standard of care medication

Study type: Interventional

Funder types: Other

Identifiers

NCT01254708

AGM201000428

Details and patient eligibility

About

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.

Full 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.

Enrollment: 4 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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4 participants in 2 patient groups

Control

Active Comparator group

Description:

Standard of care group. Medication as prescribed by the primary physician would be used by this group. Such medications might include azoles as voriconazole

Treatment:

Drug: Regular standard of care medication

liposomal amphotericin B (AmBisome ®)

Experimental group

Description:

Inhaled Liposomal preparation of Amphotericin B.

Treatment:

Drug: Ambisome ®