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Sponsored by: |
National Heart, Lung, and Blood Institute (NHLBI) |
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Information provided by: | National Heart, Lung, and Blood Institute (NHLBI) |
ClinicalTrials.gov Identifier: | NCT00268515 |
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 | Intervention | Phase |
---|---|---|
Lung Diseases |
Drug: cyclosporine Drug: tacrolimus Drug: prednisone Drug: azathioprine |
Phase II |
Study Type: | Interventional |
Study Design: | Prevention, Double-Blind, Placebo Control |
Study Start Date: | April 1998 |
Estimated Study Completion Date: | March 2003 |
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.
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
No eligibility criteria
Study ID Numbers: | 349 |
Study First Received: | December 21, 2005 |
Last Updated: | May 5, 2006 |
ClinicalTrials.gov Identifier: | NCT00268515 History of Changes |
Health Authority: | United States: Federal Government |
Anti-Inflammatory Agents Antimetabolites Prednisone Anti-Infective Agents Cyclosporine Antineoplastic Agents, Hormonal Immunologic Factors Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Tacrolimus |
Hormones Glucocorticoids Cyclosporins Immunosuppressive Agents Azathioprine Respiratory Tract Diseases Lung Diseases Antifungal Agents Antirheumatic Agents |
Anti-Inflammatory Agents Antimetabolites Prednisone Anti-Infective Agents Antimetabolites, Antineoplastic Cyclosporine Molecular Mechanisms of Pharmacological Action Immunologic Factors Antineoplastic Agents Physiological Effects of Drugs Hormones, Hormone Substitutes, and Hormone Antagonists Tacrolimus Cyclosporins |
Hormones Azathioprine Respiratory Tract Diseases Therapeutic Uses Antifungal Agents Dermatologic Agents Antineoplastic Agents, Hormonal Enzyme Inhibitors Immunosuppressive Agents Glucocorticoids Pharmacologic Actions Lung Diseases Antirheumatic Agents |