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Aerosol Cyclosporine for Prevention of Lung Rejection

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ClinicalTrials.gov Identifier: NCT00268515
Recruitment Status : Completed
First Posted : December 22, 2005
Last Update Posted : May 13, 2016
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Lung Diseases Drug: cyclosporine Drug: tacrolimus Drug: prednisone Drug: azathioprine Phase 2

Detailed Description:


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.


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.

The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record

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Study Type : Interventional  (Clinical Trial)
Masking: Double
Primary Purpose: Prevention
Study Start Date : April 1998
Actual Study Completion Date : March 2003

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 100 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
No eligibility criteria

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00268515

Sponsors and Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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OverallOfficial: Aldo Iacono University of Pittsburgh
Publications of Results:
Other Publications:
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ClinicalTrials.gov Identifier: NCT00268515    
Other Study ID Numbers: 349
R01HL059490 ( U.S. NIH Grant/Contract )
First Posted: December 22, 2005    Key Record Dates
Last Update Posted: May 13, 2016
Last Verified: December 2005
Additional relevant MeSH terms:
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Lung Diseases
Respiratory Tract Diseases
Anti-Inflammatory Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Calcineurin Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Antimetabolites, Antineoplastic