Aerosol Cyclosporine for Prevention of Lung Rejection

This study has been completed.
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00268515
First received: December 21, 2005
Last updated: May 5, 2006
Last verified: December 2005

December 21, 2005
May 5, 2006
April 1998
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Complete list of historical versions of study NCT00268515 on ClinicalTrials.gov Archive Site
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Aerosol Cyclosporine for Prevention of Lung Rejection
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To evaluate the efficacy of aerosolized cyclosporine given in addition to the standard oral immunosuppressive drug regimen, in preventing acute rejection immediately after lung transplantation

BACKGROUND:

Success with lung transplantation has largely been due to the introduction of cyclosporine which has proved effective in controlling lung allograft rejection. Nevertheless, acute and chronic rejection are prevalent in spite of immunosuppressive drug regimens based on oral cyclosporine. In fact, rejection is more common in recipients of lung allografts than those who receive other solid organs. Acute rejection is treated with pulsed methylprednisolone and anti-lymphocyte globulin and consequently recipients are subject to increased risk of infection and drug toxicity. The hypothesis tested in the study was that delivery of cyclosporine to the transplanted lung by aerosol inhalation would achieve higher concentrations of cyclosporine in the graft than when it was delivered via the bloodstream and that higher concentrations in the graft would prevent rejection more effectively than systemic immune suppression with the same or reduced toxicity.

Cellular rejection occured in over 90% of the patients within the first year and often progressed to obliterative bronchiolitis (OB) which was the most common cause of death one year after transplant. In 1988, the lung transplant group at the University of Pittsburgh decided to pursue cyclosporine aerosol for the treatment for acute rejection. After animal testing, initial human experiments were performed, which suggested that cyclosporine aerosol decreased the prevalence of acute rejection and the development of obliterative bronchiolitis.

DESIGN NARRATIVE:

This prospective double blind randomized trial was designed to evaluate the efficacy of cyclosporine aerosol versus placebo aerosol as an adjuvant to oral immunosuppression with tacrolimus, prednisone, and azathioprine. The hypotheses tested included: 1) acute rejection would be lower in the patients receiving cyclosporine aerosol, 2) maintenance cyclosporine aerosol would result in reduced incidence of OB, 3) cytokines and chemokine release would be suppressed, 4) patients receiving cyclosporine aerosol would require less systemic immunosuppression and 5) there would be a lower incidence of opportunistic and bacterial infections as a consequence of more effective immunosuppressive therapy. Another specific aim of the study was to determine the optimal dose of cyclosporine aerosol that reduced rejection and/or OB and to correlate radioisotopically labeled inhalation studies with more easily measurable indices that affected the deposition of aerosolized medications.

Interventional
Phase 2
Masking: Double-Blind
Primary Purpose: Prevention
Lung Diseases
  • Drug: cyclosporine
  • Drug: tacrolimus
  • Drug: prednisone
  • Drug: azathioprine
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
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March 2003
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No eligibility criteria

Both
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No
Contact information is only displayed when the study is recruiting subjects
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NCT00268515
349
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National Heart, Lung, and Blood Institute (NHLBI)
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Investigator: Aldo Iacono University of Pittsburgh
National Heart, Lung, and Blood Institute (NHLBI)
December 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP