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Study has been placed on hold due to unavailability of funding.
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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.
In this pilot study, our main aims are:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control | Active Comparator | Standard of care group. Medication as prescribed by the primary physician would be used by this group. Such medications might include azoles as voriconazole |
|
| liposomal amphotericin B (AmBisome ®) | Experimental | Inhaled Liposomal preparation of Amphotericin B. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ambisome ® | Drug | liposomal amphotericin B |
| |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Shahid Husain, M.D M.Sc | University Health Network, Toronto | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Health Network/ Toronto General Hospital | Toronto | Ontario | M5G 2N2 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 6364439 | Background | Newman SP, Clarke SW. Therapeutic aerosols 1--physical and practical considerations. Thorax. 1983 Dec;38(12):881-6. doi: 10.1136/thx.38.12.881. No abstract available. | |
| 8795674 | Background | Barry PW, O'Callaghan C. Inhalational drug delivery from seven different spacer devices. Thorax. 1996 Aug;51(8):835-40. doi: 10.1136/thx.51.8.835. |
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| ID | Term |
|---|---|
| C068538 | liposomal amphotericin B |
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| Regular standard of care medication |
| Drug |
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 |
|
| 1 year |
| 11744410 | Background | Monforte V, Roman A, Gavalda J, Bravo C, Tenorio L, Ferrer A, Maestre J, Morell F. Nebulized amphotericin B prophylaxis for Aspergillus infection in lung transplantation: study of risk factors. J Heart Lung Transplant. 2001 Dec;20(12):1274-81. doi: 10.1016/s1053-2498(01)00364-3. |
| 10334143 | Background | Calvo V, Borro JM, Morales P, Morcillo A, Vicente R, Tarrazona V, Paris F. Antifungal prophylaxis during the early postoperative period of lung transplantation. Valencia Lung Transplant Group. Chest. 1999 May;115(5):1301-4. doi: 10.1378/chest.115.5.1301. |
| 9021176 | Background | Cicogna CE, White MH, Bernard EM, Ishimura T, Sun M, Tong WP, Armstrong D. Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother. 1997 Feb;41(2):259-61. doi: 10.1128/AAC.41.2.259. |
| 14742987 | Background | Drew RH, Dodds Ashley E, Benjamin DK Jr, Duane Davis R, Palmer SM, Perfect JR. Comparative safety of amphotericin B lipid complex and amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation. 2004 Jan 27;77(2):232-7. doi: 10.1097/01.TP.0000101516.08327.A9. |
| 11502995 | Background | Palmer SM, Drew RH, Whitehouse JD, Tapson VF, Davis RD, McConnell RR, Kanj SS, Perfect JR. Safety of aerosolized amphotericin B lipid complex in lung transplant recipients. Transplantation. 2001 Aug 15;72(3):545-8. doi: 10.1097/00007890-200108150-00036. |
| 10339471 | Background | Schwartz S, Behre G, Heinemann V, Wandt H, Schilling E, Arning M, Trittin A, Kern WV, Boenisch O, Bosse D, Lenz K, Ludwig WD, Hiddemann W, Siegert W, Beyer J. Aerosolized amphotericin B inhalations as prophylaxis of invasive aspergillus infections during prolonged neutropenia: results of a prospective randomized multicenter trial. Blood. 1999 Jun 1;93(11):3654-61. |
| 17049064 | Background | Corcoran TE, Venkataramanan R, Mihelc KM, Marcinkowski AL, Ou J, McCook BM, Weber L, Carey ME, Paterson DL, Pilewski JM, McCurry KR, Husain S. Aerosol deposition of lipid complex amphotericin-B (Abelcet) in lung transplant recipients. Am J Transplant. 2006 Nov;6(11):2765-73. doi: 10.1111/j.1600-6143.2006.01529.x. |
| 12792517 | Background | Monforte V, Roman A, Gavalda J, Lopez R, Pou L, Simo M, Aguade S, Soriano B, Bravo C, Morell F. Nebulized amphotericin B concentration and distribution in the respiratory tract of lung-transplanted patients. Transplantation. 2003 May 15;75(9):1571-4. doi: 10.1097/01.TP.0000054233.60100.7A. |