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Comparison of Sirolimus and Azathioprine in Lung Transplantation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00321906
Recruitment Status : Completed
First Posted : May 4, 2006
Results First Posted : February 4, 2014
Last Update Posted : September 21, 2016
Sponsor:
Collaborators:
Astellas Pharma Inc
Loyola University
University of Florida
University of Pennsylvania
Baylor College of Medicine
Ochsner Health System
Columbia University
University of Wisconsin, Madison
Information provided by (Responsible Party):
University of Chicago

Brief Summary:
The purpose of this study is to compare the safety and effectiveness of two different anti-rejection drug regimens.

Condition or disease Intervention/treatment Phase
Delayed Graft Function Acute Graft Rejection Drug: azathioprine Drug: sirolimus Phase 4

Detailed Description:

This multicenter prospective, randomized controlled clinical trial compared the open label use of sirolimus with that of azathioprine in a tacrolimus-based immunosuppression regimen. Eligible patients were identified during a 90-day screening period immediately after transplantation and randomized via a computer-generated scheme. Patient randomization was stratified according to center and rejection status in the first 90 days after transplantation. All patients received IL-2 receptor antagonist induction therapy, tacrolimus, azathioprine, and corticosteroids until 90 days after transplantation. At 90 days after transplantation, patients were randomized at a 1:1 ratio to either continue azathioprine or change from azathioprine to sirolimus.

The dosing and levels of immunosuppressive medications were standardized for all patients included in this study. Tacrolimus was dosed at 0.04 mg/kg twice daily with target trough levels between 5 and 15 ng/ml, azathioprine was administered at 2 mg/kg daily with dose adjustments for leukopenia, sirolimus was initially dosed at 2 mg/day with target trough levels between 5 and 15 ng/ml, and prednisone was tapered to not more than 10 mg/day by 3 months after transplantation. All patients received induction therapy with either daclizumab or basiliximab as per the product package insert.

In addition, prophylactic antimicrobials were standardized among the participating sites. All patients with either donor and/or recipient cytomegalovirus (CMV)-positive serostatus received either intravenous ganciclovir or oral valganciclovir for a total of 90 days. Lung transplant recipients who were negative for both donor and recipient CMV serostatus received valacyclovir for 90 days. Antifungal prophylaxis was determined by each site. Pneumocystis jiroveci prophylaxis was continued throughout the study. Lipid-lowering medications were recommended according to the National Cholesterol Education Program guidelines.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen Versus Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation
Study Start Date : April 2002
Actual Primary Completion Date : August 2011
Actual Study Completion Date : August 2011

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Azathioprine
(tacrolimus,azathioprine/prednisone)
Drug: azathioprine
azathioprine 2mg/kg

Active Comparator: Sirolimus
tacrolimus/sirolimus/prednisone
Drug: sirolimus
sirolimus 2-4mg daily




Primary Outcome Measures :
  1. Acute Rejection Rate at 12 Months [ Time Frame: 12mos ]
    Raw proportion of patients that experienced acute rejection at or before 12 months.


Secondary Outcome Measures :
  1. Acute Rejection-free Survival at 12 Months [ Time Frame: 12 mos ]

    Kaplan-Meier estimate of proportion of patients that had not experienced acute rejection by 12 months. Acute rejection is defined as rejection at any of the following grades.

    Grade A0 - None With/Without Grade A1 - Minimal Grade A2 - Mild Grade A3 - Moderate


  2. Severity of Acute Rejection at 12 Months [ Time Frame: 12 mos ]

    Raw proportion of patients that experienced rejection at or above grade A2 by 12 months.

    Grade A0 - None With/Without Grade A1 - Minimal Grade A2 - Mild Grade A3 - Moderate


  3. Bronchiolitis Obliterans Syndrome (BOS) at 24 Months [ Time Frame: 24 mos ]
    Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 24 months.

  4. Bronchiolitis Obliterans Syndrome (BOS) at 36 Months [ Time Frame: 36 mos ]
    Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 36 months.

  5. Overall Survival at 12 Months [ Time Frame: 12 mos ]
    Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 12 months.

  6. Overall Survival at 24 Months [ Time Frame: 24 mos ]
    Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 24 months.

  7. Overall Survival at 36 Months [ Time Frame: 36 mos ]
    Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 36 months.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Lung transplant recipients between the age of 18 and 65 years of age.
  • Females who are capable of becoming pregnant must have a negative pregnancy test prior to consent. (Females of childbearing potential must be using a medically acceptable method of birth control for the duration of the study.)
  • All patients must be able to give written informed consent.

Exclusion Criteria:

  • White blood cell count (WBC) < 4.0/mm3
  • Platelet count < 100,000/mm3
  • Severe hypercholesterolemia (> 350 mg/dl) or hypertriglyceridemia (> 500 mg/dl)
  • Uncontrolled systemic infection at the time of consent.
  • Previous organ transplant
  • Treatment with a drug within the last 30 days that has not received regulatory approval at the time of study entry or for the duration of the study (3 years).
  • Use of maintenance immunosuppression other than daclizumab, tacrolimus, azathioprine, or prednisone prior to randomization.

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): NCT00321906


Locations
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United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
Sponsors and Collaborators
University of Chicago
Astellas Pharma Inc
Loyola University
University of Florida
University of Pennsylvania
Baylor College of Medicine
Ochsner Health System
Columbia University
University of Wisconsin, Madison
Investigators
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Principal Investigator: Edward Garrity, MD University of Chicago
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT00321906    
Other Study ID Numbers: 14467B
First Posted: May 4, 2006    Key Record Dates
Results First Posted: February 4, 2014
Last Update Posted: September 21, 2016
Last Verified: September 2016
Keywords provided by University of Chicago:
Rejection in lung transplant
Additional relevant MeSH terms:
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Delayed Graft Function
Pathologic Processes
Sirolimus
Azathioprine
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antirheumatic Agents