Kidney TransplantationPhase 2NCT00076570
Combination Drug Therapy Followed by Single Drug Steroid Free Therapy to Prevent Organ Rejection in Kidney Transplantation
A Phase 2 study testing Sirolimus and Tacrolimus in people with Kidney Transplantation, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
This study will test the safety and effectiveness of a combination of three drugs followed by long-term treatment with just one drug in preventing organ rejection in kidney transplant patients. Current anti-rejection medicines are not completely effective in preventing rejection. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Sirolimus and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Aug 2012
- Phase
- Phase 2
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Candidates for a kidney transplant at the Clinical Center.
- Willingness and legal ability to give informed consent.
- Availability of donor tissue for testing. This could include splenic or peripheral blood lymphocytes from a cadaveric donor or a willing living donor who consents to periodic phlebotomy for peripheral blood lymphocyte isolation.
Who cannot join
- Immunosuppressive drug therapy at the time of or 2 months prior to enrollment. Specifically, candidates may not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive.
- Any active malignancy or any history of any hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are appropriately treated prior to transplant.
- Any known immunodeficiency syndrome, or other condition that, in the opinion of the investigators, would likely increase the risk of protocol participation or confound the interpretation of the data.
- Any history of sensitization to rabbits or extensive exposure to rabbits, as defined by symptomatic allergic response upon exposure to rabbits.
- Inability or unwillingness to comply with protocol monitoring and therapy including, among others, a history of noncompliance, circumstances where compliance with protocol requirements is not feasible due to living conditions, travel restrictions, access to urgent medical services, or access to anti-rejection drugs after the research protocol is completed.
- Peak Panel Reactive Antibody greater than 20%, or historically positive crossmatch due to HLA (human leukocyte antigen)-specific antibodies.
- HLA (human leukocyte antigen) identity between the donor and recipient.
- Pregnancy or unwillingness to practice an approved method of birth control. Acceptable methods of birth control may include barrier methods (condom and/or diaphragm with spermicide), oral contraceptives, Norplant, Depo-Provera or partner sterility.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Depletion Induction With Rabbit Anti-Thymocyte Globulin, Followed by Two Approaches Toward Monotherapy Immunosuppression in Kidney Transplant Recipients
This study will test the safety and effectiveness of a combination of three drugs followed by long-term treatment with just one drug in preventing organ rejection in kidney transplant patients. Current anti-rejection medicines are not completely effective in preventing rejection. This trial will test how well Thymoglobulin, Tacrolimus, and Sirolimus work together post-transplant and if the treatment can be reduced over time to control rejection with either Tacrolimus or Sirolimus alone.
Candidates for kidney transplantation at the National Institutes of Health Clinical Center may participate in this 5-year study. Patients will be screened for eligibility with a medical history, physical examination, and blood tests.
Read more
Participants will undergo the following tests and procedures:
- Central line placement: A large intravenous catheter (plastic tube, or IV line) is placed in a vein in the chest or neck under local anesthesia before the transplant surgery. The line remains in place for some time during the hospitalization to administer Thymoglobulin, antibiotics, and blood, if needed. The line is also used to collect blood samples.
- Leukapheresis: This procedure for collecting white blood cells is done before the transplant. The cells are studied to evaluate the patient's immune system. Whole blood is withdrawn through a catheter in an arm vein or through the central line and directed into a machine that separates the blood components by spinning. The white cells are removed and the red cells and plasma are returned to the body.
- Kidney transplant: Patients undergo kidney transplant surgery under general anesthesia.
- Immunosuppressive therapy: Patients receive thymoglobulin by vein for 4 days starting 1 day before the transplant. They also take Tylenol, Benadryl and a steroid (methylprednisolone) to help reduce the side effects of the Thymoglobulin. After the transplant, patients receive Tacrolimus and Sirolimus by mouth once a day for 6 months and then either Tacrolimus or Sirolimus alone indefinitely. In addition, they take medicines to help prevent viral and fungal infections for 6 months because the immunosuppressive therapy leaves them vulnerable to infection.
- Follow-up visits: After hospital discharge, patients return to the Clinical Center twice a week for 4 weeks, then every 6 months for 1 year, and then yearly for another 4 years. At each visit, the patient's vital signs are checked and blood and urine samples are collected. Periodically, patients are also questioned about how they feel and how the transplant has affected their quality of life. Kidney biopsies (removal of a small amount of kidney tissue through a thin needle) are done when the patient begins single-drug immunosuppression (generally 6 months after transplantation) and 1 year after that. The biopsied tissue is examined to evaluate how well the kidney is responding to the treatment and to determine how to proceed with therapy.
- Routine laboratory tests: Routine tests, coordinated by the patient's local physician, are done 2 to 3 times a week for the first 2 to 3 months after transplantation, then weekly for several more months, and at least monthly for life.
Read the detailed description
This protocol facilitates the development of methods for determining whether transplant recipients have developed immune hyporesponsiveness or tolerance towards their allograft. These methods will involve the study of peripheral blood or biopsy tissue obtained at regular intervals from patients receiving kidney or combined kidney-pancreas allografts at the NIH Clinical Center. In addition, patients that have previously received a kidney or combined kidney-pancreas allograft will be evaluated using assays requiring peripheral blood mononuclear cells and/or biopsies. Assays developed under this protocol will be used in subsequent protocols to assess the effects of immune modulating treatment regimens and may eventually be used to direct clinical care or guide the withdrawal of immunosuppressive agents. However, patients enrolled in this protocol will not have any change in treatment based solely on the assays developed without being enrolled in an additional study.
- Conditions
- Kidney Transplantation
- Being tested
- Sirolimus, Tacrolimus
- Keywords
- Tolerance, Kidney, Transplant, Polyclonal, Antibody, Kidney Transplant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
TacrolimusDrug
| Study group | Role | What they receive |
|---|---|---|
| Sirolimus | Experimental | Patients are treated with combination therapy with both sirolimus and tacrolimus for 6 month. After 6 months, patients are switched to sirolimus monotherapy and followed up for 4 years. Receives: Drug: Sirolimus |
| Tacrolimus | Active comparator | Patients are treated with combination therapy with both sirolimus and tacrolimus for 6 month. After 6 months, patients are switched to tacrolimus monotherapy and followed up for 4 years. Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Rate of Allograft Rejection
Measured: 3 years
Secondary outcomes (1)
The Rate of Significant Drug-associated Complications.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2004 (estimated)
- Study startJan 2004
- Primary completionAug 2012
- Study completionAug 2012
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 (3)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Monique E Cho, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00076570
- Sponsor's protocol ID
- 040099
- Other IDs
- 04-DK-0099
- Status last verified
- Aug 2013
- First submitted
- 26 Jan 2004
- Last updated
- 16 Oct 2013
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Eggers PW. Effect of transplantation on the Medicare end-stage renal disease program. N Engl J Med. 1988 Jan 28;318(4):223-9. doi: 10.1056/NEJM198801283180406.
PubMed 3275896Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med. 2000 Mar 2;342(9):605-12. doi: 10.1056/NEJM200003023420901.
PubMed 10699159Barry JM. Immunosuppressive drugs in renal transplantation. A review of the regimens. Drugs. 1992 Oct;44(4):554-66. doi: 10.2165/00003495-199244040-00003.
PubMed 1281071
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Depletion Induction With Rabbit Anti-Thymocyte Globulin, Followed by Two Approaches Toward Monotherapy Immunosuppression in Kidney Transplant Recipients
- ClinicalTrials.gov ID
- NCT00076570
- Acronym / sponsor ID
- 040099
- Conditions
- Kidney Transplantation
- Keywords
- Tolerance, Kidney, Transplant, Polyclonal, Antibody, Kidney Transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- Jan 2004
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 27 Jan 2004 (estimated)
- Results
- Posted 16 Oct 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test the safety and effectiveness of a combination of three drugs followed by long-term treatment with just one drug in preventing organ rejection in kidney transplant patients. Current anti-rejection medicines are not completely effective in preventing rejection. This trial will test how well Thymoglobulin, Tacrolimus, and Sirolimus work together post-transplant and if the treatment can be reduced over time to control rejection with either Tacrolimus or Sirolimus alone.
Candidates for kidney transplantation at the National Institutes of Health Clinical Center may participate in this 5-year study. Patients will be screened for eligibility with a medical history, physical examination, and blood tests.
Participants will undergo the following tests and procedures:
- Central line placement: A large intravenous catheter (plastic tube, or IV line) is placed in a vein in the chest or neck under local anesthesia before the transplant surgery. The line remains in place for some time during the hospitalization to administer Thymoglobulin, antibiotics, and blood, if needed. The line is also used to collect blood samples.
- Leukapheresis: This procedure for collecting white blood cells is done before the transplant. The cells are studied to evaluate the patient's immune system. Whole blood is withdrawn through a catheter in an arm vein or through the central line and directed into a machine that separates the blood components by spinning. The white cells are removed and the red cells and plasma are returned to the body.
- Kidney transplant: Patients undergo kidney transplant surgery under general anesthesia.
- Immunosuppressive therapy: Patients receive thymoglobulin by vein for 4 days starting 1 day before the transplant. They also take Tylenol, Benadryl and a steroid (methylprednisolone) to help reduce the side effects of the Thymoglobulin. After the transplant, patients receive Tacrolimus and Sirolimus by mouth once a day for 6 months and then either Tacrolimus or Sirolimus alone indefinitely. In addition, they take medicines to help prevent viral and fungal infections for 6 months because the immunosuppressive therapy leaves them vulnerable to infection.
- Follow-up visits: After hospital discharge, patients return to the Clinical Center twice a week for 4 weeks, then every 6 months for 1 year, and then yearly for another 4 years. At each visit, the patient's vital signs are checked and blood and urine samples are collected. Periodically, patients are also questioned about how they feel and how the transplant has affected their quality of life. Kidney biopsies (removal of a small amount of kidney tissue through a thin needle) are done when the patient begins single-drug immunosuppression (generally 6 months after transplantation) and 1 year after that. The biopsied tissue is examined to evaluate how well the kidney is responding to the treatment and to determine how to proceed with therapy.
- Routine laboratory tests: Routine tests, coordinated by the patient's local physician, are done 2 to 3 times a week for the first 2 to 3 months after transplantation, then weekly for several more months, and at least monthly for life.
Detailed description
This protocol facilitates the development of methods for determining whether transplant recipients have developed immune hyporesponsiveness or tolerance towards their allograft. These methods will involve the study of peripheral blood or biopsy tissue obtained at regular intervals from patients receiving kidney or combined kidney-pancreas allografts at the NIH Clinical Center. In addition, patients that have previously received a kidney or combined kidney-pancreas allograft will be evaluated using assays requiring peripheral blood mononuclear cells and/or biopsies. Assays developed under this protocol will be used in subsequent protocols to assess the effects of immune modulating treatment regimens and may eventually be used to direct clinical care or guide the withdrawal of immunosuppressive agents. However, patients enrolled in this protocol will not have any change in treatment based solely on the assays developed without being enrolled in an additional study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sirolimus | Experimental | Drug: SirolimusPatients are treated with combination therapy with both sirolimus and tacrolimus for 6 month. After 6 months, patients are switched to sirolimus monotherapy and followed up for 4 years. |
| Tacrolimus | Active comparator | Drug: TacrolimusPatients are treated with combination therapy with both sirolimus and tacrolimus for 6 month. After 6 months, patients are switched to tacrolimus monotherapy and followed up for 4 years. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Candidates for a kidney transplant at the Clinical Center.
- Willingness and legal ability to give informed consent.
- Availability of donor tissue for testing. This could include splenic or peripheral blood lymphocytes from a cadaveric donor or a willing living donor who consents to periodic phlebotomy for peripheral blood lymphocyte isolation.
Key exclusion criteria (8 listed)
- Immunosuppressive drug therapy at the time of or 2 months prior to enrollment. Specifically, candidates may not be taking prednisone, cyclosporine, tacrolimus, azathioprine, mycophenolate mofetil, anti-lymphocyte agents, cyclophosphamide, methotrexate, or other agents whose therapeutic effect is immunosuppressive.
- Any active malignancy or any history of any hematogenous malignancy or lymphoma. Patients with primary, cutaneous basal cell or squamous cell cancers may be enrolled providing the lesions are appropriately treated prior to transplant.
- Any known immunodeficiency syndrome, or other condition that, in the opinion of the investigators, would likely increase the risk of protocol participation or confound the interpretation of the data.
- Any history of sensitization to rabbits or extensive exposure to rabbits, as defined by symptomatic allergic response upon exposure to rabbits.
- Inability or unwillingness to comply with protocol monitoring and therapy including, among others, a history of noncompliance, circumstances where compliance with protocol requirements is not feasible due to living conditions, travel restrictions, access to urgent medical services, or access to anti-rejection drugs after the research protocol is completed.
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 |
|---|---|---|
| Sirolimus | Drug | Sirolimus |
| Tacrolimus | Drug | Tacrolimus |
Primary outcome
The Rate of Allograft Rejection
Time frame: 3 years
1 secondary outcome
The Rate of Significant Drug-associated Complications.
Time frame: 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 3275896Eggers PW. Effect of transplantation on the Medicare end-stage renal disease program. N Engl J Med. 1988 Jan 28;318(4):223-9. doi: 10.1056/NEJM198801283180406.
- Background: PubMed 10699159Hariharan S, Johnson CP, Bresnahan BA, Taranto SE, McIntosh MJ, Stablein D. Improved graft survival after renal transplantation in the United States, 1988 to 1996. N Engl J Med. 2000 Mar 2;342(9):605-12. doi: 10.1056/NEJM200003023420901.
- Background: PubMed 1281071Barry JM. Immunosuppressive drugs in renal transplantation. A review of the regimens. Drugs. 1992 Oct;44(4):554-66. doi: 10.2165/00003495-199244040-00003.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Monique E Cho, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sirolimus and Tacrolimus in people with Kidney Transplantation, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 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 8 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 16 Oct 2013. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Oct 2013). 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?
The Rate of Allograft Rejection (time frame: 3 years). 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 NCT00076570, which also lists 3 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 16 Oct 2013.