Pancreas TransplantationPhase 4NCT00693446
A Study To Compare Sirolimus Versus Tacrolimus In De Novo Simultaneous Pancreas- Kidney Allograft Recipients Receiving An Induction Therapy With Antithymocyte Globulin Plus Mycophenolate Mofetil Plus Corticosteroids
A Phase 4 study testing Sirolimus and Tacrolimus in people with Pancreas Transplantation and Kidney Transplantation, run by Nantes University Hospital at 1 site in France.
Trial summary
Experience with tacrolimus in pancreas transplantation has become a standard for immunosuppression in almost all pancreas centers over the world. Several centers have shown very good results in simultaneous pancreas-kidney (SPK) transplant recipients receiving antithymocyte globulin induction and maintenance… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Pancreas Transplantation, Kidney Transplantation
- What is being tested?
- Sirolimus and Tacrolimus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 118 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2004to Apr 2017
- 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 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Recipient age ≥ 18 and ≤ 60 years.
- Patients receiving a first cadaveric simultaneous pancreas-kidney transplant for insulin-dependent diabetes associated with end-stage renal disease.
- Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation.
- Signed and dated informed consent.
Who cannot join
- Donor age ≤ 15 years and ≥ 60 years.
- Evidence of active systemic or localized major infection.
- Evidence of infiltrate, cavitation, or consolidation on chest x-ray.
- Use of any investigational drug or treatment (in particular immuno-suppressive drugs) up to 4 weeks prior to enrollment to the study and during the 12-month treatment phase.
- History of malignancy (with the exception of adequately treated localized squamous cell or basal cell carcinoma, without recurrence within 5 years of enrolment into the study).
- Graft from a living donor.
Show all 16Show fewer
- Double renal graft.
- Pregnancy.
- Known hypersensitivity to sirolimus and its derivatives or to tacrolimus.
- Known hypersensitivity to rabbit's proteins.
- Multiple organ transplants or recipients of previously transplanted organs other than kidney.
- Treatment with cisapride (PrépulsidÒ), pimozide (OrapÒ), ketoconazole (NizoralÒ), fluconazole (TriflucanÒ) or millepertuis (ProcalmilÒ, Arkogélules MillepertuisÒ), that is not discontinued within 24 hours prior to transplant.
- Total white blood cell count ≤ 2 x 109/L or platelet count ≤ 70.000/mm3 at baseline.
- Patients with evidence of active histological or biological hepatic disease during the six months period before the transplantation.
- HIV positive recipients.
- Non-heart beating donor.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Comparative, Randomized, Prospective Study To Compare Sirolimus Versus Tacrolimus In De Novo Simultaneous Pancreas- Kidney Allograft Recipients Receiving An Induction Therapy With Antithymocyte Globulin Plus Mycophenolate Mofetil Plus Corticosteroids
Experience with tacrolimus in pancreas transplantation has become a standard for immunosuppression in almost all pancreas centers over the world. Several centers have shown very good results in simultaneous pancreas-kidney (SPK) transplant recipients receiving antithymocyte globulin induction and maintenance immunosuppression consisting of calcineurin inhibitor and mycophenolate mofetil with or without corticosteroids.
The use of sirolimus in SPK transplant patients has for the moment only been studied, with good results, in association with tacrolimus or cyclospsorine (CsA). In renal transplantation, there is also evidence that sirolimus (Rapamune) is a potent immunosuppressant that significantly reduces the incidence of acute rejection when given with CsA, effective as base therapy in the post-induction period. Because of Rapamune's effectiveness and different safety profile, it might be advantageous in terms of reduced nephrotoxicity to avoid completely calcineurin inhibitors without increased incidence of acute rejection.
To explore this further, the following study is designed to assess the use of SRL versus TAC, both treatment groups including rATG plus MMF and a 3-month course of steroids in de novo simultaneous pancreas-kidney transplant recipients.
Read the detailed description
The main objective is to compare renal and pancreas graft survivals at 12 months after simultaneous pancreas-kidney transplantation in patients receiving either a regimen combining sirolimus (SRL) plus mycophenolate mofetil (MMF) following an antibody induction (rATG) or a regimen combining tacrolimus (TAC) plus mycophenolate mofetil following an antibody induction (rATG). In both regimens corticosteroids (CS) will be withdrawn three months after transplantation.
In addition, the two treatment groups will be compared for acute rejection, renal and pancreas functions and patient survival after transplantation at 12 months and for a total period of 5 years of follow-up.
- Conditions
- Pancreas Transplantation, Kidney Transplantation
- Being tested
- Sirolimus, Tacrolimus
- Keywords
- Pancreas-kidney allograft, tacrolimus, sirolimus, Pancreas-kidney allograft recipients
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
In a first period, the patient will receive Tacrolimus. The time of first administration will be within the first 48H post transplantation. The initial dose will be 0,1 mg/day po. then titrated to maintain trough whole-blood concentrations between 5-15 ng/ml.
In a second period, the patient will receive Sirolimus. The time of first administration of Sirolimus will be between day 60 and day 90 post transplant. Tacrolimus will be stopped at that time.
The initial dose will be 8 mg/day po. till a trough level is obtained and then titrated to maintain trough whole-blood concentrations between 5-15ng/ml.
The dose of sirolimus will be administrated once a day.
TacrolimusDrug
Patients receive Tacrolimus from day 0 to the end of the study. The time of first administration will be within the first 48 hours post transplant.
The dose of tacrolimus will be administrated twice a day. The initial dose will be 0,1 mg/day po. then titrated to maintain trough whole-blood concentrations between 5-15 ng/ml.
Patients receive also rATG , mycophenolate mofetil and corticosteroids.
| Study group | Role | What they receive |
|---|---|---|
| 2 | Other | In a first period, the patient will receive Tacrolimus. The time of first administration will be within the first 48H post transplantation.
In a second period, the patient will receive Sirolimus. The time of first administration of Sirolimus will be between day 60 and day 90 post transplant. Tacrolimus will be stopped at that time. Receives: Drug: Sirolimus |
| 1 | Other | Patients receive Tacrolimus from day 0 to the end of the study (Arm Tacrolimus). Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Kidney graft and pancreas graft survivals at month 12.
Measured: 12 months
Secondary outcomes (24)
Incidence of histologically proven acute rejection episode at 3, 6, 12 months then annually up to 60 months.
Measured: 60 months
Incidence of presumed clinical acute rejection at 3, 6, 12 months then annually up to 60 months.
Measured: 60 months
Incidence of patient survival at 12 months then annually up to 60 months.
Measured: 60 months
Incidence of renal graft survival annually up to 60 months.
Measured: 60 months
Incidence of pancreas graft survival annually up to 60 months.
Measured: 60 months
Time to the first acute rejection episode (time to the beginning of treatment of acute rejection episode).
Severity of rejection episodes including a histological grade of the first acute rejection episode.
Incidence of documented infection (culture, biopsy or serologically confirmed) or presumptive infection, including opportunistic infections at 3, 6, 12 months then annually up to 60 months.
Measured: 60 months
Incidence of histologically-confirmed lymphoproliferative disease or malignancy at 12 months then annually up to 60 months.
Measured: 60 months
Renal function assessed by creatinine clearance (Cockroft and Gault's formula) at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Renal function assessed by serum creatinine at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Incidence of renal Delayed Graft Function (DGF) defined as the need for more than one dialysis during the first week following transplantation.
Duration of renal Delayed Graft Function.
Incidence of renal Slow Graft Function (SGF) defined as serum creatinine ≥ 250 µmol/l at day 5 after transplantation (in the absence of dialysis).
Histology of renal graft will be assessed at month 12 if biopsy is not contra-indicated.
Measured: At month 12
Pancreas graft function evaluated by hemoglobin A1C (HbA1C) at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Pancreas graft function evaluated by basal glycemia at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Pancreas graft function evaluated by stimulated glycemia levels at 6 and 12 months then annually up to 60 months.
Measured: 60 months
Pancreas graft function evaluated by basal insulin secretion at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Pancreas graft function evaluated by stimulated insulin secretion at 6 and 12 months then annually up to 60 months.
Measured: 60 months
Incidence of hypertension (defined as systolic ≥ 140 mmgHG and/or diastolic ≥ 90 mmgHG and the use of antihypertensive medications including diuretics) at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Number of antihypertensive drugs at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Lipid levels (cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol) at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Number of lipid lowering agents at 3, 6 and 12 months then annually up to 60 months.
Measured: 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2008 (estimated)
- Study startApr 2004
- Primary completionApr 2013
- Study completionApr 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pancreas TransplantationStudies of the same condition, open and under way.
- More trials run by Nantes University 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 118 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Diego CANTAROVICH, Doctor, Principal investigator, Nantes University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00693446
- Sponsor's protocol ID
- BRD/04/2-D
- Status last verified
- May 2015
- First submitted
- 5 Jun 2008
- Last updated
- 12 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Cantarovich D, Kervella D, Karam G, Dantal J, Blancho G, Giral M, Garandeau C, Houzet A, Ville S, Branchereau J, Delbos F, Guillot-Gueguen C, Volteau C, Leroy M, Renaudin K, Soulillou JP, Hourmant M. Tacrolimus- versus sirolimus-based immunosuppression after simultaneous pancreas and kidney transplantation: 5-year results of a randomized trial. Am J Transplant. 2020 Jun;20(6):1679-1690. doi: 10.1111/ajt.15809. Epub 2020 Feb 28.
PubMed 32022990
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Comparative, Randomized, Prospective Study To Compare Sirolimus Versus Tacrolimus In De Novo Simultaneous Pancreas- Kidney Allograft Recipients Receiving An Induction Therapy With Antithymocyte Globulin Plus Mycophenolate Mofetil Plus Corticosteroids
- ClinicalTrials.gov ID
- NCT00693446
- Acronym / sponsor ID
- BRD/04/2-D
- Conditions
- Pancreas Transplantation, Kidney Transplantation
- Keywords
- Pancreas-kidney allograft, tacrolimus, sirolimus, Pancreas-kidney allograft recipients
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 118 participants (estimated)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- Apr 2004
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2017 (estimated)
- First posted
- 9 Jun 2008 (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.
Experience with tacrolimus in pancreas transplantation has become a standard for immunosuppression in almost all pancreas centers over the world. Several centers have shown very good results in simultaneous pancreas-kidney (SPK) transplant recipients receiving antithymocyte globulin induction and maintenance immunosuppression consisting of calcineurin inhibitor and mycophenolate mofetil with or without corticosteroids.
The use of sirolimus in SPK transplant patients has for the moment only been studied, with good results, in association with tacrolimus or cyclospsorine (CsA). In renal transplantation, there is also evidence that sirolimus (Rapamune) is a potent immunosuppressant that significantly reduces the incidence of acute rejection when given with CsA, effective as base therapy in the post-induction period. Because of Rapamune's effectiveness and different safety profile, it might be advantageous in terms of reduced nephrotoxicity to avoid completely calcineurin inhibitors without increased incidence of acute rejection.
To explore this further, the following study is designed to assess the use of SRL versus TAC, both treatment groups including rATG plus MMF and a 3-month course of steroids in de novo simultaneous pancreas-kidney transplant recipients.
Detailed description
The main objective is to compare renal and pancreas graft survivals at 12 months after simultaneous pancreas-kidney transplantation in patients receiving either a regimen combining sirolimus (SRL) plus mycophenolate mofetil (MMF) following an antibody induction (rATG) or a regimen combining tacrolimus (TAC) plus mycophenolate mofetil following an antibody induction (rATG). In both regimens corticosteroids (CS) will be withdrawn three months after transplantation.
In addition, the two treatment groups will be compared for acute rejection, renal and pancreas functions and patient survival after transplantation at 12 months and for a total period of 5 years of follow-up.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 2 | Other | Drug: SirolimusIn a first period, the patient will receive Tacrolimus. The time of first administration will be within the first 48H post transplantation. In a second period, the patient will receive Sirolimus. The time of first administration of Sirolimus will be between day 60 and day 90 post transplant. Tacrolimus will be stopped at that time. |
| 1 | Other | Drug: TacrolimusPatients receive Tacrolimus from day 0 to the end of the study (Arm Tacrolimus). |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Recipient age ≥ 18 and ≤ 60 years.
- Patients receiving a first cadaveric simultaneous pancreas-kidney transplant for insulin-dependent diabetes associated with end-stage renal disease.
- Women who are of childbearing potential must have a negative serum pregnancy test and agree to use a medically acceptable method of contraception throughout the treatment period and for 3 months following discontinuation.
- Signed and dated informed consent.
Key exclusion criteria (16 listed)
- Donor age ≤ 15 years and ≥ 60 years.
- Evidence of active systemic or localized major infection.
- Evidence of infiltrate, cavitation, or consolidation on chest x-ray.
- Use of any investigational drug or treatment (in particular immuno-suppressive drugs) up to 4 weeks prior to enrollment to the study and during the 12-month treatment phase.
- History of malignancy (with the exception of adequately treated localized squamous cell or basal cell carcinoma, without recurrence within 5 years of enrolment into the study).
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 |
|---|---|---|
| SirolimusIn a first period, the patient will receive Tacrolimus. The time of first administration will be within the first 48H post transplantation. The initial dose will be 0,1 mg/day po. then titrated to maintain trough whole-blood concentrations between 5-15 ng/ml. In a second period, the patient will receive Sirolimus. The time of first administration of Sirolimus will be between day 60 and day 90 post transplant. Tacrolimus will be stopped at that time. The initial dose will be 8 mg/day po. till a trough level is obtained and then titrated to maintain trough whole-blood concentrations between 5-15ng/ml. The dose of sirolimus will be administrated once a day. | Drug | 2 |
| TacrolimusPatients receive Tacrolimus from day 0 to the end of the study. The time of first administration will be within the first 48 hours post transplant. The dose of tacrolimus will be administrated twice a day. The initial dose will be 0,1 mg/day po. then titrated to maintain trough whole-blood concentrations between 5-15 ng/ml. Patients receive also rATG , mycophenolate mofetil and corticosteroids. | Drug | 1 |
Primary outcome
Kidney graft and pancreas graft survivals at month 12.
Time frame: 12 months
24 secondary outcomes
Incidence of histologically proven acute rejection episode at 3, 6, 12 months then annually up to 60 months.
Time frame: 60 months
Incidence of presumed clinical acute rejection at 3, 6, 12 months then annually up to 60 months.
Time frame: 60 months
Incidence of patient survival at 12 months then annually up to 60 months.
Time frame: 60 months
Incidence of renal graft survival annually up to 60 months.
Time frame: 60 months
Incidence of pancreas graft survival annually up to 60 months.
Time frame: 60 months
Time to the first acute rejection episode (time to the beginning of treatment of acute rejection episode).
Severity of rejection episodes including a histological grade of the first acute rejection episode.
Incidence of documented infection (culture, biopsy or serologically confirmed) or presumptive infection, including opportunistic infections at 3, 6, 12 months then annually up to 60 months.
Time frame: 60 months
Incidence of histologically-confirmed lymphoproliferative disease or malignancy at 12 months then annually up to 60 months.
Time frame: 60 months
Renal function assessed by creatinine clearance (Cockroft and Gault's formula) at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Renal function assessed by serum creatinine at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Incidence of renal Delayed Graft Function (DGF) defined as the need for more than one dialysis during the first week following transplantation.
Duration of renal Delayed Graft Function.
Incidence of renal Slow Graft Function (SGF) defined as serum creatinine ≥ 250 µmol/l at day 5 after transplantation (in the absence of dialysis).
Histology of renal graft will be assessed at month 12 if biopsy is not contra-indicated.
Time frame: At month 12
Pancreas graft function evaluated by hemoglobin A1C (HbA1C) at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Pancreas graft function evaluated by basal glycemia at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Pancreas graft function evaluated by stimulated glycemia levels at 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Pancreas graft function evaluated by basal insulin secretion at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Pancreas graft function evaluated by stimulated insulin secretion at 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Incidence of hypertension (defined as systolic ≥ 140 mmgHG and/or diastolic ≥ 90 mmgHG and the use of antihypertensive medications including diuretics) at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Number of antihypertensive drugs at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Lipid levels (cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol) at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Number of lipid lowering agents at 3, 6 and 12 months then annually up to 60 months.
Time frame: 60 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2015.
- Derived from this study: PubMed 32022990Cantarovich D, Kervella D, Karam G, Dantal J, Blancho G, Giral M, Garandeau C, Houzet A, Ville S, Branchereau J, Delbos F, Guillot-Gueguen C, Volteau C, Leroy M, Renaudin K, Soulillou JP, Hourmant M. Tacrolimus- versus sirolimus-based immunosuppression after simultaneous pancreas and kidney transplantation: 5-year results of a randomized trial. Am J Transplant. 2020 Jun;20(6):1679-1690. doi: 10.1111/ajt.15809. Epub 2020 Feb 28.
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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.
Diego CANTAROVICH, Doctor principal investigator
Nantes University Hospital
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 and Tacrolimus in people with Pancreas Transplantation and Kidney Transplantation, run by Nantes University Hospital at 1 site in France.
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 16 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 12 May 2015. 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 France. 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?
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?
Kidney graft and pancreas graft survivals at month 12. (time frame: 12 months). 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 NCT00693446, which also lists 1 linked publication.
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 12 May 2015.