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Comparison of Sirolimus and Azathioprine in Lung Transplantation

Primary Purpose

Delayed Graft Function, Acute Graft Rejection

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
azathioprine
sirolimus
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Delayed Graft Function focused on measuring Rejection in lung transplant

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Chicago

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Azathioprine

Sirolimus

Arm Description

(tacrolimus,azathioprine/prednisone)

tacrolimus/sirolimus/prednisone

Outcomes

Primary Outcome Measures

Acute Rejection Rate at 12 Months
Raw proportion of patients that experienced acute rejection at or before 12 months.

Secondary Outcome Measures

Acute Rejection-free Survival at 12 Months
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
Severity of Acute Rejection at 12 Months
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
Bronchiolitis Obliterans Syndrome (BOS) at 24 Months
Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 24 months.
Bronchiolitis Obliterans Syndrome (BOS) at 36 Months
Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 36 months.
Overall Survival at 12 Months
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 12 months.
Overall Survival at 24 Months
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 24 months.
Overall Survival at 36 Months
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 36 months.

Full Information

First Posted
May 2, 2006
Last Updated
September 19, 2016
Sponsor
University of Chicago
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
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1. Study Identification

Unique Protocol Identification Number
NCT00321906
Brief Title
Comparison of Sirolimus and Azathioprine in Lung Transplantation
Official Title
Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen Versus Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
April 2002 (undefined)
Primary Completion Date
August 2011 (Actual)
Study Completion Date
August 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago
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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Delayed Graft Function, Acute Graft Rejection
Keywords
Rejection in lung transplant

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
181 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Azathioprine
Arm Type
Active Comparator
Arm Description
(tacrolimus,azathioprine/prednisone)
Arm Title
Sirolimus
Arm Type
Active Comparator
Arm Description
tacrolimus/sirolimus/prednisone
Intervention Type
Drug
Intervention Name(s)
azathioprine
Intervention Description
azathioprine 2mg/kg
Intervention Type
Drug
Intervention Name(s)
sirolimus
Intervention Description
sirolimus 2-4mg daily
Primary Outcome Measure Information:
Title
Acute Rejection Rate at 12 Months
Description
Raw proportion of patients that experienced acute rejection at or before 12 months.
Time Frame
12mos
Secondary Outcome Measure Information:
Title
Acute Rejection-free Survival at 12 Months
Description
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
Time Frame
12 mos
Title
Severity of Acute Rejection at 12 Months
Description
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
Time Frame
12 mos
Title
Bronchiolitis Obliterans Syndrome (BOS) at 24 Months
Description
Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 24 months.
Time Frame
24 mos
Title
Bronchiolitis Obliterans Syndrome (BOS) at 36 Months
Description
Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 36 months.
Time Frame
36 mos
Title
Overall Survival at 12 Months
Description
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 12 months.
Time Frame
12 mos
Title
Overall Survival at 24 Months
Description
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 24 months.
Time Frame
24 mos
Title
Overall Survival at 36 Months
Description
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 36 months.
Time Frame
36 mos

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Garrity, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20833822
Citation
Bhorade S, Ahya VN, Baz MA, Valentine VG, Arcasoy SM, Love RB, Seethamraju H, Alex CG, Bag R, Deoliveira NC, Husain A, Vigneswaran WT, Charbeneau J, Krishnan JA, Durazo-Arvizu R, Norwick L, Garrity E. Comparison of sirolimus with azathioprine in a tacrolimus-based immunosuppressive regimen in lung transplantation. Am J Respir Crit Care Med. 2011 Feb 1;183(3):379-87. doi: 10.1164/rccm.201005-0775OC. Epub 2010 Sep 10.
Results Reference
result
PubMed Identifier
23370547
Citation
Bhorade SM, Husain AN, Liao C, Li LC, Ahya VN, Baz MA, Valentine VG, Love RB, Seethamraju H, Alex CG, Bag R, DeOliveira NC, Vigneswaran WT, Garrity ER, Arcasoy SM. Interobserver variability in grading transbronchial lung biopsy specimens after lung transplantation. Chest. 2013 Jun;143(6):1717-1724. doi: 10.1378/chest.12-2107.
Results Reference
derived

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Comparison of Sirolimus and Azathioprine in Lung Transplantation

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