Sirolimus vs Mycophenolate With Tacrolimus in Simultaneous Pancreas and Kidney Transplantation

NCT ID: NCT03582878

Last Updated: 2021-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 238 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-01
• Study Completion Date: 2019-01-01

Brief Summary

This is prospective randomized open single center clinical study to compare effect of sirolimus vs mycophenolate tacrolimus based protocol on pancreas and kidney graft survival in simultaneous pancreas and kidney recipients.

Detailed Description

MTOR (mammalian target of rapamycin) inhibitors represent group of immunosuppressive drugs with mechanism of T-cell blockade complementary to calcineurin inhibitors. The investigators presume that combination of sirolimus with tacrolimus will result in better survival of pancreatic and kidney grafts in simultaneous pancreas and kidney transplantations.

The study is proposed as a single-center extension of EUROSPK 002 trial originally started in 2004 by the EUROSPK Study Group. Recruitment of recipients started in 2004 with approval of EUROSPK 002. The patient recruitment has continued in a single center (Institute for Clinical and Experimental Medicine in Prague, Czech Republic) using the same inclusion and exclusion criteria. The recipients of primary kidney and pancreas transplantation have been randomized into 2 arms.

• In the intervention arm sirolimus is added to protocol at a dose of 5 mg immediately before transplantation, the dose is adjusted to maintained trough sirolimus trough levels between 5-10ng/ml.
• In the control arm mycophenolate mofetil was added to tacrolimus. Starting with 1g before transplantation, the dose has been increased to 1g bid afterwards.

Induction protocol at day 0. consists of ATG (antithymocyte globulin)induction 8mg/kg , Tacrolimus 0.05mg/kg, Methylprednisolone 125mg. Dosing of tacrolimus has been adjusted to maintain trough levels between 5-10ng/ml. ATG was administered at 3mg/kg on days 1.-3. Steroids have been gradually tapered from a dose of 20 mg prednison orally and withdrawn by 6w after transplantation.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mycophenolate mofetil

mycophenolate mofetil dosing 1g before transplantation and 1g bid afterwards

Group Type: ACTIVE_COMPARATOR

Mycophenolate Mofetil

Intervention Type: DRUG

Mycophenolate Mofetil dosing 1g before transplantation and 1g bid afterwards

Sirolimus

Sirolimus oral product Dosing 5mg orally 2-6h before transplantation Target trough levels between 5-10ng/ml

Group Type: EXPERIMENTAL

Sirolimus Oral Product

Intervention Type: DRUG

Oral form of sirolimus, daily dosing to achieve target trough levels between 5-10ng/ml since 1.day of transplantation

Interventions

Sirolimus Oral Product

Oral form of sirolimus, daily dosing to achieve target trough levels between 5-10ng/ml since 1.day of transplantation

Intervention Type: DRUG

Mycophenolate Mofetil

Mycophenolate Mofetil dosing 1g before transplantation and 1g bid afterwards

Intervention Type: DRUG

Other Intervention Names

Rapamune; CellCept

Eligibility Criteria

Inclusion Criteria

• Type 1 diabetes mellitus
• End stage kidney failure
• Negative CDC crossmatch
• Female patients of childbearing age must have a negative pregnancy test
• Patient must have signed the Patient Informed Consent Form.
• Patient must receive a primary simultaneous pancreas/kidney (SPK) cadaver transplant,

Exclusion Criteria

• Patient is pregnant or breastfeeding.
• Patient is allergic or intolerant to Mycophenolate Mofetil, Sirolimus, ATG, Tacrolimus
• Patient has malignancy or history of malignancy, with the exception of adequately treated localized squamous cell or basal cell carcinoma, without recurrence.
• Patient has been included in another clinical trial protocol for any investigational drug within 4 weeks prior to randomization.
• Patient has any form of substance abuse or psychiatric disorder or condition, which invalidate communication.
• Severe cardiac failure or severe liver failure diagnosed at the time of transplantation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institute for Clinical and Experimental Medicine

OTHER_GOV

Sponsor Role: lead

Responsible Party

Frantisek Saudek

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Frantisek Saudek, MD

Role: PRINCIPAL_INVESTIGATOR

Institute for Clinical and Experimental Medicine

Locations

Institute for Clinical and Experimental Medicine

Prague, , Czechia

Countries

Czechia

References

Girman P, Lipar K, Kocik M, Voska L, Koznarova R, Marada T, Lanska V, Saudek F. Sirolimus vs mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study. Am J Transplant. 2020 Mar;20(3):779-787. doi: 10.1111/ajt.15622. Epub 2019 Oct 23.

Reference Type: DERIVED

PMID: 31561278 (View on PubMed)

Other Identifiers

SiroMMFStudy 1

Identifier Type: -

Identifier Source: org_study_id