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
  Purpose

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 2

Study Type: Interventional
Study Design: Masking: Double-Blind
Primary Purpose: Prevention

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Study Start Date: April 1998
Estimated Study Completion Date: March 2003
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

No eligibility criteria

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00268515

Sponsors and Collaborators
Investigators
Investigator: Aldo Iacono University of Pittsburgh
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00268515     History of Changes
Other Study ID Numbers: 349
Study First Received: December 21, 2005
Last Updated: May 5, 2006
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Lung Diseases
Respiratory Tract Diseases
Cyclosporins
Cyclosporine
Azathioprine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 16, 2014