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

NCT ID: NCT01254708

Last Updated: 2011-10-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

SUSPENDED

Clinical Phase

PHASE2

Total Enrollment

4 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-01-31

Study Completion Date

2014-01-31

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:

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.

Conditions

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Lung Transplant Recipient

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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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

Group Type ACTIVE_COMPARATOR

Regular standard of care medication

Intervention Type 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

liposomal amphotericin B (AmBisome ®)

Inhaled Liposomal preparation of Amphotericin B.

Group Type EXPERIMENTAL

Ambisome ®

Intervention Type DRUG

liposomal amphotericin B

Interventions

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Ambisome ®

liposomal amphotericin B

Intervention Type 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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Health Network, Toronto

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Shahid Husain, M.D M.Sc

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

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University Health Network/ Toronto General Hospital

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 6364439 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8795674 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11744410 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10334143 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9021176 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14742987 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11502995 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10339471 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17049064 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12792517 (View on PubMed)

Other Identifiers

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AGM201000428

Identifier Type: -

Identifier Source: org_study_id