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

Study Overview
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Brief Summary
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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
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In this pilot study, our main aims are: 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. 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.

Official Title
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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

Conditions
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Lung Transplant Recipient

Intervention / Treatment
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* Drug: Ambisome ®
* Drug: Regular standard of care medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single or double lung transplant recipients who are at least one year out of transplantation. Age >18yrs of age Able to understand and complete informed consent. Exclusion Criteria: Pregnant woman or woman capable of bearing children, who will not perform urine pregnancy test. Nursing mothers. Subjects with hypersensitivity to Amphotericin deoxycholate or liposomal Amphotericin. Subjects with a past history of bronchospasm associated with aerosol drug use. Subjects with active bacterial or viral infection as defined by the current use of non-prophylactic antibiotic anti-viral medications. Subjects treated with cytolytic medications (Campath /Thymoglobulin) within the last month. Subjects with an FEV1< 30% Predicted or FVC% <30%. Subjects requiring supplemental oxygen. Receipt of Inhaled or IV Amphotericin B within last 30 days. Subjects with known fungal infection as per MSG Criteria on therapy with antifungal drugs or diagnosed on the day of bronchoscopy. Current use of azoles active against molds (Voriconazole, itraconazole, posaconazole) for the prophylaxis. Serum creatinine > 150 mmol/L on the day of clinic visit. Liver enzymes ALT/ AST/ Alkphos greater than two times upper limit of normal. Concurrent intravenous aminoglycoside use. Subjects with fever > 38.2°C. Subjects on mechanical ventilation. Expected survival less than 6 months. Re-transplants and heart/lung transplant patients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control<br>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<br>* 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<br>|
| Experimental: liposomal amphotericin B (AmBisome ®)<br>Inhaled Liposomal preparation of Amphotericin B. | Drug: Ambisome ®<br>* liposomal amphotericin B<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Function | 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 | 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 | 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 | 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 |