Aerosol Cyclosporine for Prevention of Lung Rejection
Primary Purpose
Lung Diseases
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
cyclosporine
tacrolimus
prednisone
azathioprine
Sponsored by
About this trial
This is an interventional prevention trial for Lung Diseases
Eligibility Criteria
No eligibility criteria
Sites / Locations
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00268515
First Posted
December 21, 2005
Last Updated
May 12, 2016
Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
1. Study Identification
Unique Protocol Identification Number
NCT00268515
Brief Title
Aerosol Cyclosporine for Prevention of Lung Rejection
Study Type
Interventional
2. Study Status
Record Verification Date
December 2005
Overall Recruitment Status
Completed
Study Start Date
April 1998 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2003 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
National Heart, Lung, and Blood Institute (NHLBI)
4. Oversight
5. Study Description
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
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.
The study completion date listed in this record was obtained from the "End Date" entered in the Protocol Registration and Results System (PRS) record
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Diseases
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Masking
Double
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
tacrolimus
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Type
Drug
Intervention Name(s)
azathioprine
10. Eligibility
Sex
All
Maximum Age & Unit of Time
100 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
No eligibility criteria
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Aldo Iacono
Organizational Affiliation
University of Pittsburgh
12. IPD Sharing Statement
Citations:
PubMed Identifier
12636164
Citation
Burkart GJ, Smaldone GC, Eldon MA, Venkataramanan R, Dauber J, Zeevi A, McCurry K, McKaveney TP, Corcoran TE, Griffith BP, Iacono AT. Lung deposition and pharmacokinetics of cyclosporine after aerosolization in lung transplant patients. Pharm Res. 2003 Feb;20(2):252-6. doi: 10.1023/a:1022275222207.
Results Reference
background
PubMed Identifier
16407509
Citation
Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP. A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006 Jan 12;354(2):141-50. doi: 10.1056/NEJMoa043204.
Results Reference
result
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Aerosol Cyclosporine for Prevention of Lung Rejection
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