Glomerular Filtration RatePhase 4NCT00999258
Impact of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients
A Phase 4 study testing sirolimus in people with Glomerular Filtration Rate and Chronic Allograft Nephropathy, run by Temple University at 1 site in United States.
Trial summary
The objective of this study is to examine the effect on allograft function and histology of converting African American renal transplant recipients with chronic allograft nephropathy (CAN) from a tacrolimus-based regimen to a sirolimus-based maintenance immunosuppression regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glomerular Filtration Rate, Chronic Allograft Nephropathy
- What is being tested?
- sirolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to Jun 2011
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- African American (self-identified) renal transplant recipients.
- Primary or re-transplant kidney-only recipients.
- Recipients on tacrolimus-based immunosuppression regimen.
- Time interval after transplant: at least 3 months but not greater than 5 years.
- Renal transplant recipients with 10% decrease in GFR from baseline.
- Women of childbearing potential must have a negative pregnancy test upon enrollment, and must consent to receive contraceptive counseling and to use effective contraception while enrolled in the study. Two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method.
Who cannot join
- GFR <40ml/min.
- Urine protein-to-creatinine ratio >0.5.
- Significant chronic allograft nephropathy grade 3 Banff score.
- Evidence of acute rejection episodes within the past 3 months.
- Evidence of active infection within the past month.
- Any malignancy except treated non-melanoma skin cancer within the past 3 years.
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- Leucopenia <2,000/mm3 within the past month.
- Thrombocytopenia <100,000/mm3 within the past month.
- Total cholesterol >300mg/dl, despite adequate treatment.
- Triglycerides >500mg/dl, despite adequate treatment.
- Non-healed post-surgical or non-surgical wound.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Temple University
Philadelphia, Pennsylvania, 19140
Serban Constantinescu, MD, PhD, 217-707-9171, serban.constantinescu@tuhs.temple.edu
Serban Constantinescu, MD, PhD
About this study
Official title: Prospective Trial of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients With Chronic Allograft Nephropathy
The objective of this study is to examine the effect on allograft function and histology of converting African American renal transplant recipients with chronic allograft nephropathy (CAN) from a tacrolimus-based regimen to a sirolimus-based maintenance immunosuppression regimen.
The investigators hypothesize that the conversion from tacrolimus to sirolimus in African American renal recipients will stabilize or improve renal allograft function, and stabilize the histological progression of CAN. This conversion will have the potential to prolong long-term graft survival in African American renal transplant patients.
GFR measurements, histological parameters on the allograft biopsy, as well as patient and graft survival, incidence of acute rejection, and specific side effects will be monitored and compared between the sirolimus conversion group and the patients who will be maintained on tacrolimus.
Read the detailed description
All African American renal transplant recipients (>3months and <5 years post-transplant) at our institution that are currently on a tacrolimus based regimen will be screened. Subjects with 10% or more decrease in glomerular filtration rate (GFR) from baseline, estimated by the MDRD formula,65 and who meet all inclusion criteria will be consented to be enrolled in the study. Baseline will be defined as the highest GFR estimated by MDRD formula, within 3 months of transplant.
Subjects who consent to participate in the study will undergo allograft biopsy and GFR measurement by Gd-DTPA, and will be randomly assigned (2:1) to undergo conversion from tacrolimus to sirolimus or to continue to receive tacrolimus.
The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will be checked within a week and adjusted in a linear fashion to achieve a trough goal of 12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1 year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely. Sirolimus trough levels will be monitored in the study as follows: weekly for the first month, monthly from 1 - 6 months, every 3 months from 6 months - 1 year post conversion. Subjects will continue to receive maintenance immunosuppression consisting of mycophenolate mofetil 500mg to 1000 mg po bid as tolerated and corticosteroid taper per protocol (maintenance of 2.5mg - 5mg po daily at 6 months post-transplant and then indefinitely). GFR measurement by DTPA will be repeated at 6 months, and 1 year post conversion. The second allograft biopsy will be performed at 1 year after sirolimus conversion.
The subjects assigned to the tacrolimus maintenance group (control group) represent our present standard of care. The subjects will continue to receive prednisone, and mycophenolate mofetil, similarly to the subjects assigned to the sirolimus conversion group. In the tacrolimus maintenance group, the subjects will be monitored according to our current clinic protocol, monthly between 3 months - 1 year post transplant, every two months in the second year post-transplant and every 3 months after 2 years. The tacrolimus dose will be adjusted to achieve a trough of 5-10ng/ml in subjects randomized to the control group which is standard of care per protocol. GFR measurement by DTPA will be repeated at 6 months, and 1 year post randomization. The second allograft biopsy will be performed at 1 year post randomization.
Patient and graft survival, and the incidence of acute rejection, proteinuria, hyperlipidemia, anemia, leucopenia, thrombocytopenia, and other clinical parameters will be monitored and compared between the sirolimus conversion group and the subjects who will be maintained on tacrolimus.
- Being tested
- sirolimus
- Keywords
- glomerular filtration rate, chronic allograft nephropathy, Kidney transplantation, African American
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
Also called GFR measurements and allograft biopsies
The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will be checked within a week and adjusted in a linear fashion to achieve a trough goal of 12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1 year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely.
The subjects assigned to the tacrolimus maintenance group (control group) represent our present standard of care.
| Study group | Role | What they receive |
|---|---|---|
| sirolimus | Active comparator | the subjects will undergo conversion from tacrolimus to sirolimus OR they will continue to receive tacrolimus. Receives: Drug: sirolimus |
| tacrolimus | No intervention | Not described Receives: Drug: sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glomerular filtration rate measured by Gd-DTPA
Measured: 6 months, and 1 year
Secondary outcomes (2)
Quantification the histological markers on renal allograft biopsy
Measured: 1 year
Patient survival, graft survival, and incidence of acute rejection
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2009 (estimated)
- Study startSep 2009
- Primary completionJun 2011 (estimated)
- Study completionJun 2011 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Glomerular Filtration RateStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Temple University
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Investigators
- Serban Constantinescu, MD, PhD, Principal investigator, Temple University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00999258
- Sponsor's protocol ID
- 0468X1-4504
- Status last verified
- Oct 2009
- First submitted
- 20 Oct 2009
- Last updated
- 21 Oct 2009
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Trial of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients With Chronic Allograft Nephropathy
- ClinicalTrials.gov ID
- NCT00999258
- Acronym / sponsor ID
- 0468X1-4504
- Keywords
- glomerular filtration rate, chronic allograft nephropathy, Kidney transplantation, African American
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Temple UniversityUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer
- Study start
- Sep 2009
- Primary completion
- Jun 2011 (estimated)
- Study completion
- Jun 2011 (estimated)
- First posted
- 21 Oct 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study is to examine the effect on allograft function and histology of converting African American renal transplant recipients with chronic allograft nephropathy (CAN) from a tacrolimus-based regimen to a sirolimus-based maintenance immunosuppression regimen.
The investigators hypothesize that the conversion from tacrolimus to sirolimus in African American renal recipients will stabilize or improve renal allograft function, and stabilize the histological progression of CAN. This conversion will have the potential to prolong long-term graft survival in African American renal transplant patients.
GFR measurements, histological parameters on the allograft biopsy, as well as patient and graft survival, incidence of acute rejection, and specific side effects will be monitored and compared between the sirolimus conversion group and the patients who will be maintained on tacrolimus.
Detailed description
All African American renal transplant recipients (>3months and <5 years post-transplant) at our institution that are currently on a tacrolimus based regimen will be screened. Subjects with 10% or more decrease in glomerular filtration rate (GFR) from baseline, estimated by the MDRD formula,65 and who meet all inclusion criteria will be consented to be enrolled in the study. Baseline will be defined as the highest GFR estimated by MDRD formula, within 3 months of transplant.
Subjects who consent to participate in the study will undergo allograft biopsy and GFR measurement by Gd-DTPA, and will be randomly assigned (2:1) to undergo conversion from tacrolimus to sirolimus or to continue to receive tacrolimus.
The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will be checked within a week and adjusted in a linear fashion to achieve a trough goal of 12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1 year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely. Sirolimus trough levels will be monitored in the study as follows: weekly for the first month, monthly from 1 - 6 months, every 3 months from 6 months - 1 year post conversion. Subjects will continue to receive maintenance immunosuppression consisting of mycophenolate mofetil 500mg to 1000 mg po bid as tolerated and corticosteroid taper per protocol (maintenance of 2.5mg - 5mg po daily at 6 months post-transplant and then indefinitely). GFR measurement by DTPA will be repeated at 6 months, and 1 year post conversion. The second allograft biopsy will be performed at 1 year after sirolimus conversion.
The subjects assigned to the tacrolimus maintenance group (control group) represent our present standard of care. The subjects will continue to receive prednisone, and mycophenolate mofetil, similarly to the subjects assigned to the sirolimus conversion group. In the tacrolimus maintenance group, the subjects will be monitored according to our current clinic protocol, monthly between 3 months - 1 year post transplant, every two months in the second year post-transplant and every 3 months after 2 years. The tacrolimus dose will be adjusted to achieve a trough of 5-10ng/ml in subjects randomized to the control group which is standard of care per protocol. GFR measurement by DTPA will be repeated at 6 months, and 1 year post randomization. The second allograft biopsy will be performed at 1 year post randomization.
Patient and graft survival, and the incidence of acute rejection, proteinuria, hyperlipidemia, anemia, leucopenia, thrombocytopenia, and other clinical parameters will be monitored and compared between the sirolimus conversion group and the subjects who will be maintained on tacrolimus.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| sirolimus | Active comparator | Drug: sirolimusthe subjects will undergo conversion from tacrolimus to sirolimus OR they will continue to receive tacrolimus. |
| tacrolimus | No intervention | Drug: sirolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- African American (self-identified) renal transplant recipients.
- Primary or re-transplant kidney-only recipients.
- Recipients on tacrolimus-based immunosuppression regimen.
- Time interval after transplant: at least 3 months but not greater than 5 years.
- Renal transplant recipients with 10% decrease in GFR from baseline.
Key exclusion criteria (11 listed)
- GFR <40ml/min.
- Urine protein-to-creatinine ratio >0.5.
- Significant chronic allograft nephropathy grade 3 Banff score.
- Evidence of acute rejection episodes within the past 3 months.
- Evidence of active infection within the past month.
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 |
|---|---|---|
| sirolimusAlso: GFR measurements and allograft biopsiesThe subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will be checked within a week and adjusted in a linear fashion to achieve a trough goal of 12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1 year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely. The subjects assigned to the tacrolimus maintenance group (control group) represent our present standard of care. | Drug | sirolimus, tacrolimus |
Primary outcome
Glomerular filtration rate measured by Gd-DTPA
Time frame: 6 months, and 1 year
2 secondary outcomes
Quantification the histological markers on renal allograft biopsy
Time frame: 1 year
Patient survival, graft survival, and incidence of acute rejection
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2009.
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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.
Serban Constantinescu, MD, PhD principal investigator
Temple University
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 sirolimus in people with Glomerular Filtration Rate and Chronic Allograft Nephropathy, run by Temple University 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 6 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 21 Oct 2009. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Serban Constantinescu, MD, PhD (215-707-9171, serban.constantinescu@tuhs.temple.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glomerular filtration rate measured by Gd-DTPA (time frame: 6 months, and 1 year). 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 21 Oct 2009.