Renal TransplantCNI-WNCT02117596
Calcineurin Inhibitor Based Immunosuppression Withdrawal
A study testing Sirolimus in people with Renal Transplant, run by Pediatric Nephrology of Alabama at 4 sites in United States.
Trial summary
Damage and scarring of a transplanted kidney has become the most common cause of loss of the transplanted kidney. This kidney damage is a complex process caused by many factors including injury during obtaining and transplanting the kidney, injury from the immune system, injury from infections, and injury from drugs… Read more about this study
- Who is it for?
- Ages Up to 19 years
- Conditions the study is for
- Renal Transplant
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 4 sitesUnited States
- Study dates
- Nov 2007to Nov 2012
- Phase
- Interventional
- 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 Up to 19 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age < 19 years (up to the day of the 19th birthday)
- Panel Reactive Antibody Level (PRA) <20% (Flow cytometry method)
- Recipient of first living donor or deceased donor renal transplantation
- Signed and dated informed consent (per local IRB standards)
Who cannot join
- Recipients of multi-organ transplants (e.g. kidney/pancreas transplant, etc.)
- Peak PRA > 20% at any time
- Recipient of en-bloc kidneys
- Recipient of an organ from an HLA identical donor or a non-heart beating donor
- Pregnant or lactating
- Positive for HIV or an immunodeficiency virus
Show all 11Show fewer
- History of malignancy
- Use of investigational agents within 4 weeks prior to transplantation
- Current use of terfenadine, cisapride, astemizole, or pimozide (unless discontinued before administration of SRL)
- Known hypersensitivity to sirolimus
- Known hypersensitivity to Prograf, Cellcept, prednisone, Cremophor, HCO-60, or murine products
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia
Pediatric Nephrology of Alabama
Birmingham, Alabama, 35205
UCLA
Los Angeles, California, 90095
Stanford University
Stanford, California, 94305
About this study
Official title: Novel Pilot Trial of Sirolimus, Mycophenolate Mofetil, and Corticosteroids Versus a Historic Control Population Receiving Calcineurin Inhibitors Based Immunosuppression
Damage and scarring of a transplanted kidney has become the most common cause of loss of the transplanted kidney. This kidney damage is a complex process caused by many factors including injury during obtaining and transplanting the kidney, injury from the immune system, injury from infections, and injury from drugs used to stop rejection. This injury leads to scars that decrease the kidney's ability to function properly, and over time the kidney is lost. Prograf® (tacrolimus) has been one of the main drugs used to prevent rejection. However, when used over time it has been shown to cause chronic damage and scarring in the transplanted kidney.
The purpose of this experimental study is to determine whether children can safely be withdrawn from Prograf® after transplantation and changed to Rapamycin® (sirolimus). Recent research studies in adult transplantation have demonstrated that with the use of Rapamycin® (sirolimus), it is possible to discontinue the use of Prograf (tacrolimus) with no increase in rejection, with decreased scarring in the kidney, and with improvements in kidney function and survival of the kidney. A total of 50 children will enroll in this study at university centers around the country. This study will last about 3 years.
Read the detailed description
Advances in immunosuppressive therapies in pediatrics have been associated with rapidly falling incidence of acute rejection and improving allograft survival. In recent analyses of the NAPRTCS database, acute rejection is no longer the most common cause of hospitalization or allograft failure. Chronic rejection has now become the most common cause of allograft failure and accounts for over 35% of allograft loss. Chronic rejection is a complex clinical condition that includes both immunologic and non-immunologic causes and is more accurately referred to as Chronic Allograft Nephropathy (CAN). Although Calcineurin inhibitors (CNI) have played a central role in reducing acute rejection and improving allograft survival, it has long been shown that they contribute to interstitial fibrosis and chronic allograft nephropathy. Recent trials in adult transplantation have demonstrated that with the use of the TOR-inhibitor, Sirolimus, it is possible to withdraw Calcineurin inhibitors with no increase in rejection and with improvements in allograft function, interstitial fibrosis and long term survival (1). We hypothesize that the use of Sirolimus (SRL) in pediatric kidney transplantation will allow the withdrawal of Calcineurin inhibitor and improved kidney function and long term survival. We plan to enroll 50 patients at the time of transplantation. Patients will receive routine immunosuppression of CNI (Prograf), Mycophenolate mofetil (Cellcept) and prednisone. Those patients with normal function and no rejection episodes after 6 months of transplantation will undergo a slow conversion from Prograf to Sirolimus (Rapamune). We will then assess the rate of rejection, allograft function, fibrosis on biopsy, and allograft survival over the following 18 months.
- Conditions
- Renal Transplant
- Being tested
- Sirolimus
- Keywords
- Pediatric, Renal, Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamune, Rapamycin
- Tacrolimus (Prograf®) At 6 months post-transplantation, patients will have Prograf® tapered by 25% per week such that they will be off of this medication by 7 months post-transplantation.
- Sirolimus (Rapamune®):
At 6 months post-transplantation, all patients will be administered Sirolimus at a dose of 1.65-2.79 mg/m2/day as a tablet or liquid (administered q 12 hours).
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Other | Single arm Receives: Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
This study has a primary endpoint of allograft function as determined by Schwartz GFR at 18 months after conversion to CNI free protocol (2 years post transplantation).
Measured: 18 mos after conversion to CNI free protocol
Secondary outcomes (1)
Secondary outcomes will include biopsy proven acute rejection episodes, progression of quantitative interstitial fibrosis as determined by Sirius Red staining and digital image analysis, Allograft survival and patient survival
Measured: measured at 12 and 24 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 posted21 Apr 2014 (estimated)
- Study startNov 2007
- Primary completionNov 2012
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal TransplantStudies 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 N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pediatric Nephrology of Alabama
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, The Emmes Company, LLC
- Responsible party
- Principal investigator, Mark Benfield, MD, Pediatric Nephrology of Alabama
- Investigators
- Mark Benfield, M.D., Principal investigator, Pediatric Nephrology of Alabama
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02117596
- Sponsor's protocol ID
- CNI Withdrawal
- Acronym
- CNI-W
- Status last verified
- Apr 2014
- First submitted
- 16 Apr 2014
- Last updated
- 21 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Pilot Trial of Sirolimus, Mycophenolate Mofetil, and Corticosteroids Versus a Historic Control Population Receiving Calcineurin Inhibitors Based Immunosuppression
- ClinicalTrials.gov ID
- NCT02117596
- Acronym / sponsor ID
- CNI-W / CNI Withdrawal
- Conditions
- Renal Transplant
- Keywords
- Pediatric, Renal, Transplant
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Pediatric Nephrology of AlabamaUniversity, hospital or other
- Collaborators
- Pfizer, The Emmes Company, LLC
- Study start
- Nov 2007
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 21 Apr 2014 (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.
Damage and scarring of a transplanted kidney has become the most common cause of loss of the transplanted kidney. This kidney damage is a complex process caused by many factors including injury during obtaining and transplanting the kidney, injury from the immune system, injury from infections, and injury from drugs used to stop rejection. This injury leads to scars that decrease the kidney's ability to function properly, and over time the kidney is lost. Prograf® (tacrolimus) has been one of the main drugs used to prevent rejection. However, when used over time it has been shown to cause chronic damage and scarring in the transplanted kidney.
The purpose of this experimental study is to determine whether children can safely be withdrawn from Prograf® after transplantation and changed to Rapamycin® (sirolimus). Recent research studies in adult transplantation have demonstrated that with the use of Rapamycin® (sirolimus), it is possible to discontinue the use of Prograf (tacrolimus) with no increase in rejection, with decreased scarring in the kidney, and with improvements in kidney function and survival of the kidney. A total of 50 children will enroll in this study at university centers around the country. This study will last about 3 years.
Detailed description
Advances in immunosuppressive therapies in pediatrics have been associated with rapidly falling incidence of acute rejection and improving allograft survival. In recent analyses of the NAPRTCS database, acute rejection is no longer the most common cause of hospitalization or allograft failure. Chronic rejection has now become the most common cause of allograft failure and accounts for over 35% of allograft loss. Chronic rejection is a complex clinical condition that includes both immunologic and non-immunologic causes and is more accurately referred to as Chronic Allograft Nephropathy (CAN). Although Calcineurin inhibitors (CNI) have played a central role in reducing acute rejection and improving allograft survival, it has long been shown that they contribute to interstitial fibrosis and chronic allograft nephropathy. Recent trials in adult transplantation have demonstrated that with the use of the TOR-inhibitor, Sirolimus, it is possible to withdraw Calcineurin inhibitors with no increase in rejection and with improvements in allograft function, interstitial fibrosis and long term survival (1). We hypothesize that the use of Sirolimus (SRL) in pediatric kidney transplantation will allow the withdrawal of Calcineurin inhibitor and improved kidney function and long term survival. We plan to enroll 50 patients at the time of transplantation. Patients will receive routine immunosuppression of CNI (Prograf), Mycophenolate mofetil (Cellcept) and prednisone. Those patients with normal function and no rejection episodes after 6 months of transplantation will undergo a slow conversion from Prograf to Sirolimus (Rapamune). We will then assess the rate of rejection, allograft function, fibrosis on biopsy, and allograft survival over the following 18 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Other | Drug: SirolimusSingle arm |
Who may qualify
- Ages
- Up to 19 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Age < 19 years (up to the day of the 19th birthday)
- Panel Reactive Antibody Level (PRA) <20% (Flow cytometry method)
- Recipient of first living donor or deceased donor renal transplantation
- Signed and dated informed consent (per local IRB standards)
Key exclusion criteria (11 listed)
- Recipients of multi-organ transplants (e.g. kidney/pancreas transplant, etc.)
- Peak PRA > 20% at any time
- Recipient of en-bloc kidneys
- Recipient of an organ from an HLA identical donor or a non-heart beating donor
- Pregnant or lactating
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: Rapamune, Rapamycin1. Tacrolimus (Prograf®) At 6 months post-transplantation, patients will have Prograf® tapered by 25% per week such that they will be off of this medication by 7 months post-transplantation. 2. Sirolimus (Rapamune®): At 6 months post-transplantation, all patients will be administered Sirolimus at a dose of 1.65-2.79 mg/m2/day as a tablet or liquid (administered q 12 hours). | Drug | Sirolimus |
Primary outcome
This study has a primary endpoint of allograft function as determined by Schwartz GFR at 18 months after conversion to CNI free protocol (2 years post transplantation).
Time frame: 18 mos after conversion to CNI free protocol
1 secondary outcome
Secondary outcomes will include biopsy proven acute rejection episodes, progression of quantitative interstitial fibrosis as determined by Sirius Red staining and digital image analysis, Allograft survival and patient survival
Time frame: measured at 12 and 24 months post transplant
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2014.
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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.
Mark Benfield, M.D. principal investigator
Pediatric Nephrology of Alabama
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sirolimus in people with Renal Transplant, run by Pediatric Nephrology of Alabama at 4 sites 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 4 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: finished, as of the sponsor's last update on 21 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
This study has a primary endpoint of allograft function as determined by Schwartz GFR at 18 months after conversion to CNI free protocol (2 years post transplantation). (time frame: 18 mos after conversion to CNI free protocol). 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 Apr 2014.