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
|
- Study Details
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Delayed Graft Function Acute Graft Rejection | Drug: azathioprine Drug: sirolimus | Phase 4 |
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.
| 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 |
| 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 |
- Acute Rejection Rate at 12 Months [ Time Frame: 12mos ]Raw proportion of patients that experienced acute rejection at or before 12 months.
- 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
- 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
- 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.
- 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.
- 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.
- 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.
- 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.
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 65 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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
| United States, Illinois | |
| University of Chicago | |
| Chicago, Illinois, United States, 60637 | |
| Principal Investigator: | Edward Garrity, MD | University of Chicago |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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 |
|
Rejection in lung transplant |
|
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 |