Delayed Graft FunctionPhase 4NCT00321906
Comparison of Sirolimus and Azathioprine in Lung Transplantation
A Phase 4 study testing azathioprine and sirolimus in people with Delayed Graft Function and Acute Graft Rejection, run by University of Chicago at 1 site in United States.
Trial summary
The purpose of this study is to compare the safety and effectiveness of two different anti-rejection drug regimens. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Delayed Graft Function, Acute Graft Rejection
- What is being tested?
- azathioprine and sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 181 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2002to Aug 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen Versus Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation
The purpose of this study is to compare the safety and effectiveness of two different anti-rejection drug regimens.
Read the 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.
- Conditions
- Delayed Graft Function, Acute Graft Rejection
- Being tested
- azathioprine, sirolimus
- Keywords
- Rejection in lung transplant
- Medical subject headings
- Delayed Graft Function
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
azathioprineDrug
azathioprine 2mg/kg
sirolimusDrug
sirolimus 2-4mg daily
| Study group | Role | What they receive |
|---|---|---|
| Azathioprine | Active comparator | (tacrolimus,azathioprine/prednisone) Receives: Drug: azathioprine |
| Sirolimus | Active comparator | tacrolimus/sirolimus/prednisone Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute Rejection Rate at 12 Months
Raw proportion of patients that experienced acute rejection at or before 12 months.
Measured: 12mos
Secondary outcomes (7)
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
Measured: 12 mos
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
Measured: 12 mos
Bronchiolitis Obliterans Syndrome (BOS) at 24 Months
Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 24 months.
Measured: 24 mos
Bronchiolitis Obliterans Syndrome (BOS) at 36 Months
Kaplan-Meier estimate of proportion of patients that had not experienced BOS by 36 months.
Measured: 36 mos
Overall Survival at 12 Months
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 12 months.
Measured: 12 mos
Overall Survival at 24 Months
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 24 months.
Measured: 24 mos
Overall Survival at 36 Months
Kaplan-Meier estimate of proportion of patients that survived to (i.e., had not died by) 36 months.
Measured: 36 mos
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2006 (estimated)
- Study startApr 2002
- Primary completionAug 2011
- Study completionAug 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Delayed Graft FunctionStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 181 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Sponsor
- Investigators
- Edward Garrity, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00321906
- Sponsor's protocol ID
- 14467B
- Status last verified
- Sep 2016
- First submitted
- 2 May 2006
- Last updated
- 21 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20833822Bhorade 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.
PubMed 23370547
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen Versus Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation
- ClinicalTrials.gov ID
- NCT00321906
- Acronym / sponsor ID
- 14467B
- Conditions
- Delayed Graft Function, Acute Graft Rejection
- Keywords
- Rejection in lung transplant
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 181 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- 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
- Study start
- Apr 2002
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 4 May 2006 (estimated)
- Results
- Posted 4 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Azathioprine | Active comparator | Drug: azathioprine(tacrolimus,azathioprine/prednisone) |
| Sirolimus | Active comparator | Drug: sirolimustacrolimus/sirolimus/prednisone |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| azathioprineazathioprine 2mg/kg | Drug | Azathioprine |
| sirolimussirolimus 2-4mg daily | Drug | Sirolimus |
Primary outcome
Acute Rejection Rate at 12 Months
Time frame: 12mos
Raw proportion of patients that experienced acute rejection at or before 12 months.
7 secondary outcomes
Acute Rejection-free Survival at 12 Months
Time frame: 12 mos
Severity of Acute Rejection at 12 Months
Time frame: 12 mos
Bronchiolitis Obliterans Syndrome (BOS) at 24 Months
Time frame: 24 mos
Bronchiolitis Obliterans Syndrome (BOS) at 36 Months
Time frame: 36 mos
Overall Survival at 12 Months
Time frame: 12 mos
Overall Survival at 24 Months
Time frame: 24 mos
Overall Survival at 36 Months
Time frame: 36 mos
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20833822Bhorade 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.
- Derived from this study: PubMed 23370547Bhorade 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward Garrity, MD principal investigator
University of Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing azathioprine and sirolimus in people with Delayed Graft Function and Acute Graft Rejection, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute Rejection Rate at 12 Months (time frame: 12mos). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00321906, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2016.