End-Stage Renal DiseasePhase 3NCT00005113
A Study to Compare Treatment With Sirolimus Versus Standard Treatment in Patients Who Have Received a Kidney Transplant
A Phase 3 study testing Cyclosporine, Sirolimus and Tacrolimus in people with End-Stage Renal Disease and Kidney Transplantation, run by Boston Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to compare treatment with the new drug sirolimus (SRL) versus the standard treatment with cyclosporine (CsA) or tacrolimus in children who have received kidney transplants. SRL is a new medication that may prevent the body's immune system from rejecting organ transplants. Read more about this study
- Who is it for?
- Ages Up to 20 years
- Conditions the study is for
- End-Stage Renal Disease, Kidney Transplantation
- What is being tested?
- Cyclosporine, Sirolimus and Tacrolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 102 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 1999to Mar 2006
- Phase
- Phase 3
- 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 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Your child may be eligible for this study if he/she:
- Has received a kidney transplant.
- Has experienced 1 or more episodes of acute rejection or chronic rejection; a rejection episode must have responded to treatment and have occurred at least 30 days before study enrollment.
- Has stable kidney function at the time of study enrollment.
- Is 20 years of age or younger.
- Has written informed consent of parent or guardian if under the age of 18.
- Agrees to use birth control during the study and for 3 months following treatment.
Who cannot join
- Your child will not be eligible for this study if he/she:
- Has a history of cancer.
- Has received a multi-organ transplant (more than a kidney).
- Has an active infection.
- Has an abnormal chest X-ray.
- Cannot provide a kidney biopsy at time of study entry.
Show all 9Show fewer
- Is allergic to sirolimus.
- Has received experimental drugs within 4 weeks of study entry.
- Is pregnant.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Boston
Boston, Massachusetts, 02115
About this study
Official title: An Open-Label, Comparative Study of the Effect of Sirolimus Versus Standard Treatment on Clinical Outcomes and Histologic Progression of Allograft Nephropathy in High Risk Pediatric Renal Transplant Patients
The purpose of this study is to compare treatment with the new drug sirolimus (SRL) versus the standard treatment with cyclosporine (CsA) or tacrolimus in children who have received kidney transplants. SRL is a new medication that may prevent the body's immune system from rejecting organ transplants.
After receiving a kidney transplant, the body recognizes the donated kidney as a foreign invader and triggers the immune system to attack the kidney. This can lead to rejection of the new kidney and a failed transplant. To help reduce the risk of kidney rejection, transplant patients are given immunosuppressant drugs, which reduce the body's normal immune response and allow the transplanted organ to function. CsA or tacrolimus are two drugs that are often given to transplant patients. However, these are powerful drugs, and it can cause serious side effects and put a patient at increased risk for infections. SRL is a new drug that has been shown to reduce a transplant patient's chance of rejecting a new kidney, without serious side effects. This study is necessary to test the safety and effectiveness of SRL in children.
Read the detailed description
Successful kidney transplantation has gradually improved over the years; much of the improvement has resulted from the use of CsA. However, adequate and tolerable immunosuppression is difficult to achieve with CsA, and rejection episodes are still frequent. CsA is nephrotoxic, with drug toxicity often masking rejection episodes. Other immunosuppressant therapies can result in a range of complications, including metabolic disturbances, adrenocortical insufficiency, and increased risk for infections. Therefore, more effective drugs with less toxicity are needed to prevent acute rejection, especially in the pediatric population where the overall graft survival rate remains significantly lower when compared with that of adult transplant recipients. SRL is an immunosuppressive agent being developed for the prophylaxis of acute renal allograft rejection. SRL has a unique mechanism of action. It inhibits T and B cell activity. In Phase I and II trials in adults, SRL was generally well tolerated and exhibited no apparent nephrotoxic properties, and significantly lower rates of rejection were seen with SRL when compared to placebo.
Patients receive extensive prestudy screening, which includes a renal core biopsy, chest x-ray, bone density study, blood tests, and glomerular filtration rate (GFR). Patients are then randomly assigned to 1 of 2 study treatment groups in a 2:1 ratio (142 patients receive SRL, CsA/tacrolimus, and corticosteroids and 71 patients receive standard CsA or tacrolimus-based double or triple drug therapy). SRL is administered as an oral dose of 3 mg/m2/day. Patients are followed for 3 years on therapy, and then for 1 month of follow-up. A renal core biopsy is performed at the time of study entry and at Months 6, 18, and at early termination of patient in study. Patients undergo physical examinations and various blood tests at specified time intervals during the 37-month study period. Efficacy is assessed by comparing the composite endpoint of biopsy-proven acute rejection, graft loss, or death after 36 months of treatment. Safety is assessed by comparing the composite endpoint of graft loss or death after 36 months of treatment.
- Conditions
- End-Stage Renal Disease, Kidney Transplantation
- Being tested
- Cyclosporine, Sirolimus, Tacrolimus
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclosporineDrug
Also called CsA
Oral tablet taken daily. Dosage is dependent on weight and is titrated to target trough level.
SirolimusDrug
Also called SRL
Dosage in liquid or tablet form is dependent on body surface area and is titrated to target trough level.
TacrolimusDrug
dosage is in oral form titrated to target trough level
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive SRL, CsA/tacrolimus, and corticosteroids for up to 36 months Receives: Drug: Cyclosporine; Drug: Sirolimus; Drug: Tacrolimus |
| 2 | Experimental | Participants will receive standard CsA or tacrolimus-based double or triple drug therapy for up to 36 months Receives: Drug: Cyclosporine; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and efficacy of sirolimus
Measured: Throughout study
Secondary outcomes (6)
Composite endpoint of biopsy proven acute rejection, graft loss, or death
Measured: At Months 6, 12, and 24
Rate of clinically diagnosed acute rejection
Measured: At months 6, 12, 24, and 36
Rate of change in glomerular filtration rate
Measured: At Month 18
Mean change in volume of allograft fibrosis
Measured: At Months 6 and 18
Intragraft expression of cytokines
Measured: Throughout study
Cytokine expression and subsequent development of chronic allograft nephropathy
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2001 (estimated)
- Study startJul 1999
- Primary completionJul 2004
- Study completionMar 2006
Why it stopped: Inability to meet the accrual target of 213.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for End-Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by Boston Children's HospitalThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William Harmon, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005113
- Sponsor's protocol ID
- DAIT SRL1
- Other IDs
- DAIT 0468E1-217-US
- Status last verified
- Mar 2012
- First submitted
- 14 Apr 2000
- Last updated
- 13 Mar 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Comparative Study of the Effect of Sirolimus Versus Standard Treatment on Clinical Outcomes and Histologic Progression of Allograft Nephropathy in High Risk Pediatric Renal Transplant Patients
- ClinicalTrials.gov ID
- NCT00005113
- Acronym / sponsor ID
- DAIT SRL1
- Conditions
- End-Stage Renal Disease, Kidney Transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inability to meet the accrual target of 213.
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Boston Children's HospitalUniversity, hospital or other
- Study start
- Jul 1999
- Primary completion
- Jul 2004 (actual)
- Study completion
- Mar 2006 (actual)
- First posted
- 31 Aug 2001 (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 purpose of this study is to compare treatment with the new drug sirolimus (SRL) versus the standard treatment with cyclosporine (CsA) or tacrolimus in children who have received kidney transplants. SRL is a new medication that may prevent the body's immune system from rejecting organ transplants.
After receiving a kidney transplant, the body recognizes the donated kidney as a foreign invader and triggers the immune system to attack the kidney. This can lead to rejection of the new kidney and a failed transplant. To help reduce the risk of kidney rejection, transplant patients are given immunosuppressant drugs, which reduce the body's normal immune response and allow the transplanted organ to function. CsA or tacrolimus are two drugs that are often given to transplant patients. However, these are powerful drugs, and it can cause serious side effects and put a patient at increased risk for infections. SRL is a new drug that has been shown to reduce a transplant patient's chance of rejecting a new kidney, without serious side effects. This study is necessary to test the safety and effectiveness of SRL in children.
Detailed description
Successful kidney transplantation has gradually improved over the years; much of the improvement has resulted from the use of CsA. However, adequate and tolerable immunosuppression is difficult to achieve with CsA, and rejection episodes are still frequent. CsA is nephrotoxic, with drug toxicity often masking rejection episodes. Other immunosuppressant therapies can result in a range of complications, including metabolic disturbances, adrenocortical insufficiency, and increased risk for infections. Therefore, more effective drugs with less toxicity are needed to prevent acute rejection, especially in the pediatric population where the overall graft survival rate remains significantly lower when compared with that of adult transplant recipients. SRL is an immunosuppressive agent being developed for the prophylaxis of acute renal allograft rejection. SRL has a unique mechanism of action. It inhibits T and B cell activity. In Phase I and II trials in adults, SRL was generally well tolerated and exhibited no apparent nephrotoxic properties, and significantly lower rates of rejection were seen with SRL when compared to placebo.
Patients receive extensive prestudy screening, which includes a renal core biopsy, chest x-ray, bone density study, blood tests, and glomerular filtration rate (GFR). Patients are then randomly assigned to 1 of 2 study treatment groups in a 2:1 ratio (142 patients receive SRL, CsA/tacrolimus, and corticosteroids and 71 patients receive standard CsA or tacrolimus-based double or triple drug therapy). SRL is administered as an oral dose of 3 mg/m2/day. Patients are followed for 3 years on therapy, and then for 1 month of follow-up. A renal core biopsy is performed at the time of study entry and at Months 6, 18, and at early termination of patient in study. Patients undergo physical examinations and various blood tests at specified time intervals during the 37-month study period. Efficacy is assessed by comparing the composite endpoint of biopsy-proven acute rejection, graft loss, or death after 36 months of treatment. Safety is assessed by comparing the composite endpoint of graft loss or death after 36 months of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Cyclosporine, Drug: Sirolimus, Drug: TacrolimusParticipants will receive SRL, CsA/tacrolimus, and corticosteroids for up to 36 months |
| 2 | Experimental | Drug: Cyclosporine, Drug: TacrolimusParticipants will receive standard CsA or tacrolimus-based double or triple drug therapy for up to 36 months |
Who may qualify
- Ages
- Up to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Has received a kidney transplant.
- Has experienced 1 or more episodes of acute rejection or chronic rejection; a rejection episode must have responded to treatment and have occurred at least 30 days before study enrollment.
- Has stable kidney function at the time of study enrollment.
- Is 20 years of age or younger.
- Has written informed consent of parent or guardian if under the age of 18.
Key exclusion criteria (9 listed)
- Has a history of cancer.
- Has received a multi-organ transplant (more than a kidney).
- Has an active infection.
- Has an abnormal chest X-ray.
- Cannot provide a kidney biopsy at time of study entry.
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 |
|---|---|---|
| CyclosporineAlso: CsAOral tablet taken daily. Dosage is dependent on weight and is titrated to target trough level. | Drug | 1, 2 |
| SirolimusAlso: SRLDosage in liquid or tablet form is dependent on body surface area and is titrated to target trough level. | Drug | 1 |
| Tacrolimusdosage is in oral form titrated to target trough level | Drug | 1, 2 |
Primary outcome
Safety and efficacy of sirolimus
Time frame: Throughout study
6 secondary outcomes
Composite endpoint of biopsy proven acute rejection, graft loss, or death
Time frame: At Months 6, 12, and 24
Rate of clinically diagnosed acute rejection
Time frame: At months 6, 12, 24, and 36
Rate of change in glomerular filtration rate
Time frame: At Month 18
Mean change in volume of allograft fibrosis
Time frame: At Months 6 and 18
Intragraft expression of cytokines
Time frame: Throughout study
Cytokine expression and subsequent development of chronic allograft nephropathy
Time frame: Throughout study
Results and safety
The study was stopped early (reason given: Inability to meet the accrual target of 213.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2012.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclosporine, Sirolimus and Tacrolimus in people with End-Stage Renal Disease and Kidney Transplantation, run by Boston Children's Hospital 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 7 inclusion and 9 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: stopped early, as of the sponsor's last update on 13 Mar 2012. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Inability to meet the accrual target of 213.). Results are not available in the source record.
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?
Safety and efficacy of sirolimus (time frame: Throughout study). 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 13 Mar 2012.