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

NCT00693446 | Unknown Phase 4

• 1 other identifier: BRD/04/2-D
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Pancreas Transplantation; Kidney Transplantation

Keywords

Pancreas-kidney allograft; tacrolimus; sirolimus; Pancreas-kidney allograft recipients

Outcome Measures

Primary Outcomes (1)

• Kidney graft and pancreas graft survivals at month 12.

  12 months

Secondary Outcomes (24)

• Incidence of histologically proven acute rejection episode at 3, 6, 12 months then annually up to 60 months.

  60 months

• Incidence of presumed clinical acute rejection at 3, 6, 12 months then annually up to 60 months.

  60 months

• Incidence of patient survival at 12 months then annually up to 60 months.

  60 months

• Incidence of renal graft survival annually up to 60 months.

  60 months

• Incidence of pancreas graft survival annually up to 60 months.

  60 months

Study Arms (2)

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.

Drug: Sirolimus

1

OTHER

Patients receive Tacrolimus from day 0 to the end of the study (Arm Tacrolimus).

Drug: Tacrolimus

Interventions

Sirolimus DRUG

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.

2

Tacrolimus DRUG

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.

1

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Nantes University Hospital: lead

Study Sites (1)

CHU de Nantes

Nantes, Nantes, France

Location

Related Publications (1)

• 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.

  PMID: 32022990 DERIVED

MeSH Terms

Interventions

Sirolimus; Tacrolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Diego CANTAROVICH, Doctor

  Nantes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2008
• First Posted: June 9, 2008
• Study Start: April 1, 2004
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2017
• Last Updated: May 12, 2015

Record last verified: 2015-05

Locations

FR (1)