Acute Graft RejectionAstellasNCT01265537
A Pilot Study Comparing the Use of Low-target Versus Conventional Target Advagraf
A study testing Tacrolimus in people with Acute Graft Rejection and Diabetes, run by University of British Columbia at 1 site in Canada.
Trial summary
While the incidence of acute rejection and early graft loss have improved dramatically with the advent of newer immunosuppressant medications, improvements in long-term patient and allograft survival after kidney transplantation have not been achieved. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Acute Graft Rejection, Diabetes
- What is being tested?
- Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- 24 Jun 2011to 11 Oct 2019
- Phase
- Interventional
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients over 18 years of age who receive a deceased, living unrelated or living related donor renal transplant
- No history of pre-existing diabetes mellitus
- Not using diabetic medications (insulin, hypoglycemic agents) at the time of transplantation
- Random plasma glucose level <11.1 at the time of transplantation
- Peak PRA (panel reactive antibody) <30%
- Females capable of becoming pregnant must have a negative pregnancy test at baseline and are required to practice an approved method of birth control for the duration of the study and for a period of three months following discontinuation of study medication
- The patient has given written informed consent to participate in the study
Who cannot join
- Patients with primary non-function
- Peak PRA>=30%
- Multiple organ transplants
- HLA (human leukocyte antigen) identical living donor transplant recipients
- Cold ischemia time over 36 hours
- Nonheart beating donor kidney recipients
Show all 14Show fewer
- Pediatric donor kidney recipients
- Donor age>=65 years
- Patients who are known to have a positive hepatitis C serology, who are human immunodeficiency virus (HIV) or Hepatitis B surface antigen positive. Laboratory results obtained within 6 months prior to study entry are acceptable. Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C will be excluded.
- Patients who are Epstein-Barr virus (EBV) negative and are receiving a transplant from an EBV-positive donor (mismatch).
- Presence of any severe allergy requiring acute (within 4 weeks of baseline) or chronic treatment, or hypersensitivity to drugs similar to those used in the study
- Patients with systemic infections
- Existence of any surgical or medical condition, other than the current transplant, which in the opinion of the investigator, preclude enrollment in this trial
- Inability to cooperate or communicate with the investigator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Prospective, Open Label, Pilot Study Comparing the Use of Low-target Advagraf With Rabbit Antithymocyte Globulin Induction Versus Conventional Target Advagraf With Basiliximab Induction in a Steroid-avoidance Immunosuppressive Protocol for de Novo Renal Transplant Recipients
While the incidence of acute rejection and early graft loss have improved dramatically with the advent of newer immunosuppressant medications, improvements in long-term patient and allograft survival after kidney transplantation have not been achieved. The specific drug combination that provides the best outcomes with the least amount of side effects is not known. Each kidney transplant center uses the combination of drugs that they believe is optimal. This study is about identifying whether drugs that are currently approved for use in kidney transplantation can be used in a new combination safely and with potentially fewer side effects than the drug combinations that are currently used at St. Paul's Hospital and other transplant centres.
Read the detailed description
Purpose This study has been designed to test whether using Thymoglobulin with low dose tacrolimus and early steroid withdrawal will minimize both kidney rejection and the development of new onset diabetes after transplant (NODAT).
Justification Experimental treatment is low target tacrolimus with thymoglobulin. Standard treatment is a standard target (higher dose) tacrolimus and basiliximab, instead of thymoglobulin.
The investigators hypothesize, that a combined approach of early steroid withdrawal and low dose tacrolimus in low immunologic risk transplant recipients will be effective in reducing the incidence of new onset diabetes mellitus, while maintaining a low risk of acute rejection.
Objective
The objective of this study is to compare early post-transplant outcomes with the use of low target versus standard target Advagraf in de novo kidney allograft recipients of low immunologic risk undergoing early corticosteroid withdrawal.
Research Method
This is a pilot study. Primary and secondary outcomes are as follows:
Primary Outcome Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation.
Secondary Outcomes
- Patient survival
- Graft survival
- Frequency, severity, and treatment of hypertension
- Frequency, severity, and treatment of hyperlipidemia (serum total cholesterol, (high density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides)
- Weight gain
- Infections (cytomegalovirus (CMV), opportunistic infections including urinary tract infections requiring treatment, pneumonia)
- Malignancy, including post-transplant lymphoproliferative disease (PTLD)
- Leukopenia
- Renal function as measured by serum creatinine and estimated Glomerular Filtration Rate (eGFR)
The primary endpoint will be evaluated by time-to-event Kaplan Meier analysis and by Chi-squared analysis of final 6 month data.
Statistical Analysis
Sample size and power:
In the setting of early steroid withdrawal, Woodle et al. reported an acute rejection rate of 14% with rATG and 24% with an interleukin-2 receptor antibody induction(10). The incidence of NODAT was reported at 21% by Woodle, et al., and was reported 10% in the low dose tacrolimus arm of the ELITE-Symphony trial. The investigators, therefore expect a combined event rate of 24% in Group A and 45% in group B. With a power of 0.80 and alpha error of 0.05, the investigators determined that the investigators need 72 subjects in each arm to demonstrate a 20% difference in our composite primary outcome. For this initial pilot study, the investigators aim to recruit a total of 30 subjects After receiving informed consent, subjects will be randomized on a 1:1 basis to one of the two treatment groups. Subjects who discontinue the study prematurely will not be replaced.
- Conditions
- Acute Graft Rejection, Diabetes
- Being tested
- Tacrolimus
- Keywords
- Transplant, Tacrolimus, Diabetes after transplant, Acute rejection prevention, New onset diabetes after transplant
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Advagraf
Low target tacrolimus Advagraf (0.25mg/kg) orally once daily dosed as per manufacturer's recommendation to target trough levels as per Table 1
Table 1
Months post tx:
0-1 month, level 5-7; 1-3 months, level 4-5; and 3-6 months, level 3-4
TacrolimusDrug
Also called Advagraf
Standard dose of tacrolimus Advagraf (0.25mg/kg) orally once daily dosed as per manufacturer's recommendation to target trough levels as per Table 1
Table 1
Months post tx
0-1 month; level 8-12; 1-3 months, level 6-9; and 3-6 months, level 5-8.
| Study group | Role | What they receive |
|---|---|---|
| Low target tacrolimus (Advagraf) | Experimental | This group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. Receives: Drug: Tacrolimus |
| Standard target tacrolimus (Advagraf) | Active comparator | This group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection
Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation. NODAT will be defined as either FPG >7.0mmol/L OR symptoms of hyperglycemia and a random plasma glucose of >11.1 OR 2-h plasma glucose >11.1 during an oral glucose tolerance test(OGTT).
Measured: 6 months post transplant
Secondary outcomes (11)
Number of Participant Deaths
Death of any participant by end of study.
Measured: 6 months post transplant
Number of Participants With Graft Failure
Any graft failure by the end of the study.
Measured: 6 months post transplant
Number of Participants With Dialysis Events
Any dialysis required by end of study.
Measured: 6 months post transplant
Number of Participants With Infection Events
Any infection (CMV, opportunistic infections including urinary tract infections requiring treatment, pneumonia) by end of study.
Measured: 6 months post transplant
Number of Participants With Hospitalization Events
Any hospitalization by end of study.
Measured: 6 months post transplant
Number of Participants With Malignancy Events
Any malignancy (including post-transplant lymphoproliferative disease) by end of study.
Measured: 6 months post transplant
Number of Participants With Cardiovascular Event
Any cardiovascular events by end of study.
Measured: 6 months post transplant
Number of Any Leukopenia Events
Any leukopenia by end of study.
Measured: 6 months post transplant
Number of Leukopenia Events on ≥2 Occasions
Any leukopenia on ≥2 occasions by end of study.
Measured: 6 months post transplant
Change From Baseline in Weight
Any changes in weight by end of study.
Measured: baseline to 6 months post transplant
eGFR at 6 Months
Participant eGFR value by end of study.
Measured: 6 months post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2010 (estimated)
- Study start24 Jun 2011
- Primary completion21 Feb 2019
- Study completion11 Oct 2019
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.
- Other trials for Acute Graft RejectionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Canada, Inc.
- Responsible party
- Principal investigator, Jagbir Gill, University of British Columbia
- Investigators
- Jagbir Gill, MD, Principal investigator, UBC / Dept of Medicine / Nephrology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01265537
- Sponsor's protocol ID
- H10-03047
- Acronym
- Astellas
- Status last verified
- Jan 2025
- First submitted
- 21 Dec 2010
- Last updated
- 23 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Open Label, Pilot Study Comparing the Use of Low-target Advagraf With Rabbit Antithymocyte Globulin Induction Versus Conventional Target Advagraf With Basiliximab Induction in a Steroid-avoidance Immunosuppressive Protocol for de Novo Renal Transplant Recipients
- ClinicalTrials.gov ID
- NCT01265537
- Acronym / sponsor ID
- Astellas / H10-03047
- Conditions
- Acute Graft Rejection, Diabetes
- Keywords
- Transplant, Tacrolimus, Diabetes after transplant, Acute rejection prevention, New onset diabetes after transplant
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- Astellas Pharma Canada, Inc.
- Study start
- 24 Jun 2011 (actual)
- Primary completion
- 21 Feb 2019 (actual)
- Study completion
- 11 Oct 2019 (actual)
- First posted
- 23 Dec 2010 (estimated)
- Results
- Posted 11 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
While the incidence of acute rejection and early graft loss have improved dramatically with the advent of newer immunosuppressant medications, improvements in long-term patient and allograft survival after kidney transplantation have not been achieved. The specific drug combination that provides the best outcomes with the least amount of side effects is not known. Each kidney transplant center uses the combination of drugs that they believe is optimal. This study is about identifying whether drugs that are currently approved for use in kidney transplantation can be used in a new combination safely and with potentially fewer side effects than the drug combinations that are currently used at St. Paul's Hospital and other transplant centres.
Detailed description
Purpose This study has been designed to test whether using Thymoglobulin with low dose tacrolimus and early steroid withdrawal will minimize both kidney rejection and the development of new onset diabetes after transplant (NODAT).
Justification Experimental treatment is low target tacrolimus with thymoglobulin. Standard treatment is a standard target (higher dose) tacrolimus and basiliximab, instead of thymoglobulin.
The investigators hypothesize, that a combined approach of early steroid withdrawal and low dose tacrolimus in low immunologic risk transplant recipients will be effective in reducing the incidence of new onset diabetes mellitus, while maintaining a low risk of acute rejection.
Objective
The objective of this study is to compare early post-transplant outcomes with the use of low target versus standard target Advagraf in de novo kidney allograft recipients of low immunologic risk undergoing early corticosteroid withdrawal.
Research Method
This is a pilot study. Primary and secondary outcomes are as follows:
Primary Outcome Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation.
Secondary Outcomes
- Patient survival
- Graft survival
- Frequency, severity, and treatment of hypertension
- Frequency, severity, and treatment of hyperlipidemia (serum total cholesterol, (high density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides)
- Weight gain
- Infections (cytomegalovirus (CMV), opportunistic infections including urinary tract infections requiring treatment, pneumonia)
- Malignancy, including post-transplant lymphoproliferative disease (PTLD)
- Leukopenia
- Renal function as measured by serum creatinine and estimated Glomerular Filtration Rate (eGFR)
The primary endpoint will be evaluated by time-to-event Kaplan Meier analysis and by Chi-squared analysis of final 6 month data.
Statistical Analysis
Sample size and power:
In the setting of early steroid withdrawal, Woodle et al. reported an acute rejection rate of 14% with rATG and 24% with an interleukin-2 receptor antibody induction(10). The incidence of NODAT was reported at 21% by Woodle, et al., and was reported 10% in the low dose tacrolimus arm of the ELITE-Symphony trial. The investigators, therefore expect a combined event rate of 24% in Group A and 45% in group B. With a power of 0.80 and alpha error of 0.05, the investigators determined that the investigators need 72 subjects in each arm to demonstrate a 20% difference in our composite primary outcome. For this initial pilot study, the investigators aim to recruit a total of 30 subjects After receiving informed consent, subjects will be randomized on a 1:1 basis to one of the two treatment groups. Subjects who discontinue the study prematurely will not be replaced.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low target tacrolimus (Advagraf) | Experimental | Drug: TacrolimusThis group will receive rabbit anti-thymocyte globulin (rATG) induction (3 -4 doses of 1.5 mg/kg during the first post transplant week) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "low-target" Advagraf. |
| Standard target tacrolimus (Advagraf) | Active comparator | Drug: TacrolimusThis group will receive basiliximab induction (40 mg total) with IV solumedrol, MPA (Mycophenolate Mofetil or Mycophenolate Sodium), and "standard target" Advagraf. |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female patients over 18 years of age who receive a deceased, living unrelated or living related donor renal transplant
- No history of pre-existing diabetes mellitus
- Not using diabetic medications (insulin, hypoglycemic agents) at the time of transplantation
- Random plasma glucose level <11.1 at the time of transplantation
- Peak PRA (panel reactive antibody) <30%
Key exclusion criteria (14 listed)
- Patients with primary non-function
- Peak PRA>=30%
- Multiple organ transplants
- HLA (human leukocyte antigen) identical living donor transplant recipients
- Cold ischemia time over 36 hours
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 |
|---|---|---|
| TacrolimusAlso: AdvagrafLow target tacrolimus Advagraf (0.25mg/kg) orally once daily dosed as per manufacturer's recommendation to target trough levels as per Table 1 Table 1 Months post tx: 0-1 month, level 5-7; 1-3 months, level 4-5; and 3-6 months, level 3-4 | Drug | Low target tacrolimus (Advagraf) |
| TacrolimusAlso: AdvagrafStandard dose of tacrolimus Advagraf (0.25mg/kg) orally once daily dosed as per manufacturer's recommendation to target trough levels as per Table 1 Table 1 Months post tx 0-1 month; level 8-12; 1-3 months, level 6-9; and 3-6 months, level 5-8. | Drug | Standard target tacrolimus (Advagraf) |
Primary outcome
Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection
Time frame: 6 months post transplant
Composite endpoint of biopsy proven acute rejection and NODAT at 6 months post transplantation. NODAT will be defined as either FPG >7.0mmol/L OR symptoms of hyperglycemia and a random plasma glucose of >11.1 OR 2-h plasma glucose >11.1 during an oral glucose tolerance test(OGTT).
11 secondary outcomes
Number of Participant Deaths
Time frame: 6 months post transplant
Number of Participants With Graft Failure
Time frame: 6 months post transplant
Number of Participants With Dialysis Events
Time frame: 6 months post transplant
Number of Participants With Infection Events
Time frame: 6 months post transplant
Number of Participants With Hospitalization Events
Time frame: 6 months post transplant
Number of Participants With Malignancy Events
Time frame: 6 months post transplant
Number of Participants With Cardiovascular Event
Time frame: 6 months post transplant
Number of Any Leukopenia Events
Time frame: 6 months post transplant
Number of Leukopenia Events on ≥2 Occasions
Time frame: 6 months post transplant
Change From Baseline in Weight
Time frame: baseline to 6 months post transplant
eGFR at 6 Months
Time frame: 6 months post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jagbir Gill, MD principal investigator
UBC / Dept of Medicine / Nephrology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Tacrolimus in people with Acute Graft Rejection and Diabetes, run by University of British Columbia at 1 site in Canada.
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 7 inclusion and 14 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 23 Jan 2025. 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 Canada. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2020). 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?
Number of Participants With New Onset Diabetes After Transplant (NODAT) or Acute Rejection (time frame: 6 months post transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 23 Jan 2025.