Comparison of Sirolimus and Azathioprine in Lung Transplantation

Delayed Graft Function Clinical Trial

Official title:

Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen Versus Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00321906
• Other study ID #: 14467B
• Status: Completed
• Phase: Phase 4
• First received: May 2, 2006
• Last updated: September 19, 2016
• Start date: April 2002
• Est. completion date: August 2011

Study information

• Verified date: September 2016
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 181
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Acute Graft Rejection
• Delayed Graft Function

Intervention

Drug:
• azathioprine
azathioprine 2mg/kg
• sirolimus
sirolimus 2-4mg daily

Locations

Country	Name	City	State
United States	University of Chicago	Chicago	Illinois

Sponsors (9)

Lead Sponsor	Collaborator
University of Chicago	Astellas Pharma Inc, Baylor College of Medicine, Columbia University, Loyola University, Ochsner Health System, University of Florida, University of Pennsylvania, University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 tacroli — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Acute Rejection Rate at 12 Months	Raw proportion of patients that experienced acute rejection at or before 12 months.	12mos	No
Secondary	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	12 mos	Yes
Secondary	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	12 mos	Yes
Secondary	Bronchiolitis Obliterans Syndrome (BOS) at 24 Months	Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 24 months.	24 mos	No
Secondary	Bronchiolitis Obliterans Syndrome (BOS) at 36 Months	Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 36 months.	36 mos	No
Secondary	Overall Survival at 12 Months	Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 12 months.	12 mos	No
Secondary	Overall Survival at 24 Months	Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 24 months.	24 mos	No
Secondary	Overall Survival at 36 Months	Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 36 months.	36 mos	No