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

NCT01254708 | Suspended Phase 2

• 1 other identifier: AGM201000428
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Transplant Recipient

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Presence of Invasive fungal infection

  1 year

Study Arms (2)

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

Drug: Regular standard of care medication

liposomal amphotericin B (AmBisome ®)

EXPERIMENTAL

Inhaled Liposomal preparation of Amphotericin B.

Drug: Ambisome ®

Interventions

Ambisome ® DRUG

liposomal amphotericin B

liposomal amphotericin B (AmBisome ®)

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

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

University Health Network/ Toronto General Hospital

Toronto, Ontario, M5G 2N2, Canada

Location

Related Publications (10)

• 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.

  PMID: 6364439 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.

  PMID: 8795674 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.

  PMID: 11744410 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.

  PMID: 10334143 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.

  PMID: 9021176 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.

  PMID: 14742987 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.

  PMID: 11502995 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.

  PMID: 10339471 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.

  PMID: 17049064 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.

  PMID: 12792517 BACKGROUND

MeSH Terms

Interventions

liposomal amphotericin B

Study Officials

• Shahid Husain, M.D M.Sc

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2010
• First Posted: December 6, 2010
• Study Start: January 1, 2012
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: October 19, 2011

Record last verified: 2011-10

Locations

CA (1)